phenobarbital

Research Excerpts

Overview

Phenobarbital is an antiepileptic drug that offers a viable alternative to benzodiazepines for AWS treatment. It is a central nervous system depressant that also indirectly activates nuclear receptor constitutive active androstane receptor (CAR), which promotes drug and energy metabolism.

Excerpt	Reference	Relevance
"Phenobarbital (PB) is a commonly prescribed anti-epileptic drug that can also benefit newborns from hyperbilirubinemia. "	( Phenobarbital in Nuclear Receptor Activation: An Update. Men, S; Wang, H, 2023)	3.8
"Phenobarbital is an antiepileptic drug that offers a viable alternative to benzodiazepines for AWS treatment."	( Phenobarbital for Acute Alcohol Withdrawal Management in Surgical Trauma Patients-A Retrospective Comparison Study. Chang, Y; de Moya, M; Dijkink, S; Larentzakis, A; Levine, AR; Nejad, S; Nisavic, M; Velmahos, G, )	2.3
"Phenobarbital is a potential therapeutic option for pharmaco-resistant EMA."	( Low-dose phenobarbital for epilepsy with myoclonic absences: A case report. Ito, S; Nagata, S; Nagumo, K; Nishikawa, A; Oguni, H, 2021)	2.48
"Phenobarbital is a commonly used anticonvulsant for the treatment of canine epileptic seizures. "	( Serum NMR metabolomics uncovers multiple metabolic changes in phenobarbital-treated dogs. Lohi, H; Müller, E; Ottka, C; Weber, C, 2021)	2.3
"Phenobarbital is an inducer of cytochrome P450 (CYP) 3A, while midazolam is a CYP3A substrate."	( Phenobarbital, Midazolam Pharmacokinetics, Effectiveness, and Drug-Drug Interaction in Asphyxiated Neonates Undergoing Therapeutic Hypothermia. Cools, F; de Haan, TR; Dijk, PH; Dijkman, KP; Egberts, TCG; Favié, LMA; Groenendaal, F; Huitema, ADR; Nuytemans, DHGM; Rademaker, CMA; Rijken, M; Simons, SHP; van Bel, F; van den Broek, MPH; van der Lee, JH; van Heijst, A; van Straaten, HLM; Zecic, A; Zonnenberg, IA, 2019)	2.68
"Phenobarbital is a central nervous system depressant that also indirectly activates nuclear receptor constitutive active androstane receptor (CAR), which promotes drug and energy metabolism, as well as cell growth (and death), in the liver. "	( Phenobarbital indirectly activates the constitutive active androstane receptor (CAR) by inhibition of epidermal growth factor receptor signaling. Moore, R; Mutoh, S; Negishi, M; Pedersen, L; Perera, L; Sobhany, M; Sueyoshi, T, 2013)	3.28
"Phenobarbital (PB) is a cytochrome P450 (CYP) 2B inducer, and piperonyl butoxide (PBO) is a CYP1A/2B inducer. "	( Suppressive effect of liver tumor-promoting activities in rats subjected to combined administration of phenobarbital and piperonyl butoxide. Akane, H; Itahashi, M; Mitsumori, K; Morita, R; Nakane, F; Shibutani, M; Shiraki, A; Suzuki, K; Yafune, A, 2013)	2.05
"Phenobarbital (PB) is a non-genotoxic indirect CAR activator, which induces cytochrome P450 (CYP) and other xenobiotic metabolizing enzymes and is known to produce liver foci/tumors in mice and rats."	( Mode of action and human relevance analysis for nuclear receptor-mediated liver toxicity: A case study with phenobarbital as a model constitutive androstane receptor (CAR) activator. Bailey, J; Bars, R; Bell, D; Cattley, RC; Elcombe, CR; Ferguson, SS; Geter, D; Goetz, A; Goodman, JI; Hester, S; Jacobs, A; Lake, BG; Omiecinski, CJ; Peffer, RC; Schoeny, R; Wolf, DC; Xie, W, 2014)	1.34
"Phenobarbital is a long-acting barbiturate, which in an overdose can cause central nervous system depression, respiratory failure and haemodynamic instability; these patients can remain obtunded for many days."	( Successful use of haemodialysis to treat phenobarbital overdose. Austin, R; Hoy, M; Hoyland, K; Wildman, M, 2013)	1.38
"Phenobarbital (PB) is a prototypical nongenotoxic carcinogen that activates the constitutive androstane receptor (CAR) resulting in rodent liver tumors."	( Dose-response modeling of early molecular and cellular key events in the CAR-mediated hepatocarcinogenesis pathway. Bhat, VS; Geter, DR; Gollapudi, BB; Hester, SD; Sura, R, 2014)	1.12
"Phenobarbital is an old antiepileptic drug used in severe epilepsy. "	( High phenobarbital clearance during continuous renal replacement therapy: a case report and pharmacokinetic analysis. Rosenborg, S; Saraste, L; Wide, K, 2014)	2.36
"Phenobarbital is an effective and safe anticonvulsant drug introduced in clinical use in 1904. "	( Clinical Pharmacology of Phenobarbital in Neonates: Effects, Metabolism and Pharmacokinetics. Pacifici, GM, 2016)	2.18
"Phenobarbital is an anticonvulsive drug widely used in newborns with hypoxic-ischemic encephalopathy. "	( Effect of co-medication on the pharmacokinetic parameters of phenobarbital in asphyxiated newborns. Hronová, K; Pokorná, P; Šíma, M; Slanař, O, 2015)	2.1
"Phenobarbital is a commonly employed antidepressant and anti-epileptic drug. "	( To Analyze the Amelioration of Phenobarbital Induced Oxidative Stress by Erucin, as Indicated by Biochemical and Histological Alterations. Arora, R; Arora, S; Bhushan, S; Kaur, P; Kumar, R; Mannan, R; Sharma, R; Singh, AP; Singh, B; Vig, AP, 2016)	2.16
"Phenobarbital is a safe alternative to diazepam in the treatment of DT."	( Phenobarbital versus diazepam for delirium tremens--a retrospective study. Allerup, P; Anderson, JE; Fink-Jensen, A; Hjermø, I; Ulrichsen, J, 2010)	3.25
"Phenobarbital (PB) is a prototypical inducer for studies of xenobiotic responses in animals. "	( Hormone receptor-like in 96 and Broad-Complex modulate phenobarbital induced transcription of cytochrome P450 CYP6D1 in Drosophila S2 cells. Kozaki, T; Lin, GG; Scott, JG, 2011)	2.06
"Phenobarbital (PB) is an efficacious and well-studied hepatic tumor promoting agent. "	( Effect of vitamin E on hepatic cell proliferation and apoptosis in mice deficient in the p50 subunit of NF-κB after treatment with phenobarbital. Glauert, HP; Harp, C; Li, J; Spear, BT; Tharappel, JC, 2011)	2.02
"Phenobarbital is an effective treatment for epilepsy but concerns remain over its potential neurocognitive toxicity. "	( Cognitive and mood effects of phenobarbital treatment in people with epilepsy in rural China: a prospective study. Bell, GS; de Boer, HM; Ding, D; Hong, Z; Kwan, P; Li, S; Lin, W; Sander, JW; Sun, J; Thompson, PJ; Wang, W; Wu, J; Wu, Q; Yu, P; Zhang, Q; Zhao, Q; Zhou, D, 2012)	2.11
"Phenobarbital (PB) is an efficacious hepatic tumor promoter. "	( Vitamin E inhibits hepatic NF-kappaB activation in rats administered the hepatic tumor promoter, phenobarbital. Calfee-Mason, KG; Glauert, HP; Spear, BT, 2002)	1.97
"Phenobarbital (PB) is an antiepileptic drug that promotes hepatocarcinogenesis in rodents when administered subsequent to an initiating carcinogen like N-nitrosodiethylamine (DEN). "	( Overexpression of glutamine synthetase is associated with beta-catenin-mutations in mouse liver tumors during promotion of hepatocarcinogenesis by phenobarbital. Buchmann, A; Gaunitz, F; Gebhardt, R; Kurek, R; Loeppen, S; Schneider, D; Schwarz, M, 2002)	1.96
"Phenobarbital is a strong nongenotoxic hepatocarcinogen in B6C3F1 mice, but not in C57BL/6 mice."	( Inhibition of mouse hepatocyte gap junctional intercellular communication by phenobarbital correlates with strain-specific hepatocarcinogenesis. Fernstrom, MJ; Ruch, RJ; Warner, KA, 2003)	1.27
"Phenobarbital (PB) which is a typical inducer of CYP2B1 and 3A2 induced production of hydroxyl radicals by rat liver and ketoconazole, an inhibitor of P450, inhibited production of hydroxyl radicals in vitro."	( Role of phenobarbital-inducible cytochrome P450s as a source of active oxygen species in DNA-oxidation. Funae, Y; Hiroi, T; Imaoka, S; Minamiyama, Y; Osada, M; Takemura, S; Toyokuni, S; Yukimura, T, 2004)	1.48
"Phenobarbital is a long-acting barbiturate metabolized in the liver by the cytochrome p450 3a4 system."	( Treatment of acute tacrolimus whole-blood elevation with phenobarbital in the pediatric liver transplant recipient. Bristow, LJ; Chang, IF; Goss, JA; Karpen, SJ; Quirós-Tejeira, RE, 2005)	1.3
"Phenobarbital (PB) is a nongenotoxic rodent carcinogen which induces global hypomethylation and regions of hypermethylation in mouse liver."	( Phenobarbital induces progressive patterns of GC-rich and gene-specific altered DNA methylation in the liver of tumor-prone B6C3F1 mice. Bachman, AN; Goodman, JI; Phillips, JM, 2006)	2.5
"Phenobarbital is an effective drug for most patients with convulsive seizures and has no severe side effect."	( [Evaluation of the efficacy of phenobarbital in treatment of epilepsy in rural areas: study of 2455 patients in rural China]. Dai, XY; Hong, Z; Ma, GY; Wang, TP; Wang, WZ; Wu, JZ; Yang, B; Yuan, CL; Zhao, DH, 2006)	1.34
"Phenobarbital is a lipophilic molecule used as a sedative and antiepileptic drug that elicits a multitude of effects in the liver, including gross liver enlargement, hepatocyte hypertrophy, and induced expression of drug-metabolizing enzymes and other liver-specific genes. "	( Phenobarbital regulates nuclear expression of HNF-4alpha in mouse and rat hepatocytes independent of CAR and PXR. Bell, AW; Michalopoulos, GK, 2006)	3.22
"Phenobarbital-induced GH is a rare clinical entity which necessitates meticulous evaluation. "	( Phenobarbital-induced gingival hyperplasia. Farahani, RM; Lafzi, A; Shoja, MA, 2007)	3.23
"Phenobarbital is a drug that induces within the rat liver increased protein synthesis in the mitochondria and mitochondrial morphological shape changes."	( Chronic phenobarbital-induced mitochondrial pleomorphism in the rat liver. Almsherqi, Z; Deng, Y; McLachlan, CS; Tay, SK, 2007)	1.5
"Phenobarbital (PB) is a nongenotoxic tumor promoter in the liver. "	( Effect of phenobarbital on hepatic cell proliferation and apoptosis in mice deficient in the p50 subunit of NF-kappaB. Glauert, HP; Spear, BT; Tharappel, JC, 2008)	2.19
"Phenobarbital is an inducer of xenobiotic-metabolizing enzymes, such as cytochrome P-450, glutathione S-transferases (GSTs) and NAD(P)H:quinone reductase, as well as being a promoter of hepatocarcinogenesis. "	( Phenobarbital induction of AP-1 binding activity mediates activation of glutathione S-transferase and quinone reductase gene expression. Bergelson, S; Daniel, V; Pinkus, R, 1993)	3.17
"Phenobarbital (PB) is a potent tumor promoter in rodent liver. "	( Phenobarbital selectively promotes initiated cells with reduced TGF beta receptor levels. Boyer, IJ; De Souza, AT; Hankins, GR; Jirtle, RL; Mansbach, JM; Mills, JJ, 1996)	3.18
"Phenobarbital (PB) is a potent inducer of cytochrome P450 enzymes, particularly CYP2B1/2B2. "	( In vivo phenobarbital treatment increases protein binding to a putative AP-1 site in the CYP2B2 promoter. Blouin, RA; Howard, G; Roe, AL, 1996)	2.17
"Phenobarbital (PB) is a classical inducer of drug metabolizing enzymes and known to stimulate liver growth transiently in rodents. "	( Phenobarbital transiently stimulates uptake of 2-aminoisobutyric acid in hepatocytes. Leibold, E; Schwarz, LR, 1996)	3.18
"Phenobarbital (PB) is an archetypal representative for chemicals including industrial solvents, pesticides, plant products, and clinically used drugs that induce several genes within CYP subfamilies 2B, 2A, 2C, and 3A in rodents and humans."	( Characterization of a phenobarbital-responsive enhancer module in mouse P450 Cyp2b10 gene. Honkakoski, P; Negishi, M, 1997)	1.33
"Phenobarbital is an efficacious tumor-promoting agent in the liver. "	( Effect of phenobarbital on hepatic eicosanoid concentrations in rats. Glauert, HP; Peebles, RS, 1997)	2.14
"Phenobarbital (PB) also is a hepatic tumor promoter that produces a different natural history than peroxisome proliferators during the promotion of hepatocarcinogenesis."	( Lack of correlation between hepatic prostaglandin concentrations and DNA synthesis after the administration of phenobarbital and the peroxisome proliferator ciprofibrate in rats. Glauert, HP; Leung, LK, 1997)	1.23
"Phenobarbital is a classical inducer of the drug metabolizing cytochrome P450 genes, but the molecular mechanism of induction has not been elucidated. "	( Phenobarbital alters protein binding to the CYP2B1/2 phenobarbital-responsive unit in native chromatin. Kemper, B; Kim, J, 1997)	3.18
"Phenobarbital is a well-known inducer of bilirubin-metabolizing enzymes in the liver."	( Effect of phenobarbital on bilirubin metabolism in rat brain. Hansen, TW; Tommarello, S, 1998)	1.42
"Phenobarbital is a better discriminant when dosing is every 24 hours as with artesunate, rather than the 8-hourly regimen for quinine-tetracycline."	( Initial evaluation of low-dose phenobarbital as an indicator of compliance with antimalarial drug treatment. Feely, M; Fungladda, W; Hay, A; Karbwang, J; Pickard, CE; Shires, S, 1998)	1.31
"Phenobarbital (PB) is a non-genotoxic liver tumor promoter used extensively in initiation-promotion protocols. "	( Phenobarbital promotes liver growth in c-myc/TGF-alpha transgenic mice by inducing hypertrophy and inhibiting apoptosis. Sanders, S; Thorgeirsson, SS, 1999)	3.19
"Phenobarbital (PB) is a prototype for a class of agents that produce marked transcriptional activation of a number of genes, including certain cytochrome P-450s. "	( Phenobarbital responsiveness conferred by the 5'-flanking region of the rat CYP2B2 gene in transgenic mice. Beck, NB; Omiecinski, CJ; Ramsden, R; Sommer, KM, 1999)	3.19
"Phenobarbital (PHE) is a liver carcinogen in B6C3F1 mice and a weak mutagen that does not appear to form DNA adducts. "	( Subchronic administration of phenobarbital alters the mutation spectrum of lacI in the livers of Big Blue transgenic mice. Cunningham, ML; deBoer, JG; Glickman, BW; Shane, BS; Smith-Dunn, DL, 2000)	2.04
"Phenobarbital is a well studied inducer of P450s in insects and it induced expression of CYP6D3 mRNA in both the CS (16-fold) and LPR (1.6 fold) strains."	( Expression and regulation of CYP6D3 in the house fly, Musca domestica (L.). Kasai, S; Scott, JG, 2001)	1.03
"Phenobarbital (PB) is an antiepileptic drug which promotes hepatocarcinogenesis in rodents when administered subsequent to an initiating carcinogen like diethylnitrosamine (DEN)."	( Selective pressure during tumor promotion by phenobarbital leads to clonal outgrowth of beta-catenin-mutated mouse liver tumors. Aydinlik, H; Buchmann, A; Moennikes, O; Nguyen, TD; Schwarz, M, 2001)	1.29
"Phenobarbital (PB) is a well characterized inducer of cytochrome P450 (P450) 2B and 3A subfamilies. "	( Enhanced induction of cytochrome P450 enzymes and CAR binding in TNF (p55(-/-)/p75(-/-)) double receptor knockout mice following phenobarbital treatment. Blouin, RA; Mattson, MP; Van Ess, PJ, 2002)	1.96
"Phenobarbital is a potent inhibitor of aldehyde reductase, inhibiting both substrate and cofactor non-competitively (Ki = 80.4 +/- 10.5 micrometer and 66.9 +/- 1.6 micrometer respectively)."	( Kinetics and mechanism of action of aldehyde reductase from pig kidney. Davidson, WS; Flynn, TG, 1979)	0.98
"Phenobarbital is know to be a stimulator of the drug metabolizing enzyme system in the liver."	( [The effect of primidone treatment of thyroid hormones in epileptic children and adolescents (author's transl)]. Fichsel, H; Knöpfle, G, 1977)	0.98
"Phenobarbital: --Is a "safe" anticonvulsant: steady serum level during 24 hours periods in chronic treatment and rather stable relationship between ingested dose and serum level."	( [Serum phenobarbital levels in epileptics]. Brachet, A; Henry, P; Loiseau, P, 1975)	1.43
"Phenobarbital is a long-acting barbiturate often prescribed for seizure disorders. "	( Acute phenobarbital intoxication. Cunningham, A; Lindberg, MC; Lindberg, NH, 1992)	2.21
"Phenobarbital (PB) is an effective growth stimulator of hepatic hyperplastic nodules developed with diethylnitrosamine and 2-acetylaminofluorene plus partial hepatectomy (the Solt-Farber model), but it does not apparently stimulate the growth of preneoplastic lesions produced with aflatoxin B1 (AFB). "	( Differential regulation of cytochrome(s) P450 2B1/2 by phenobarbital in hepatic hyperplastic nodules induced by aflatoxin B1 or diethylnitrosamine plus 2-acetylaminofluorene in male F344 rats. Chen, ZY; Eaton, DL, 1991)	1.97
"Phenobarbital is a potent inducer of several liver-specific genes such as those encoding detoxication enzymes, including cytochromes P450. "	( Effect of phenobarbital on the glucocorticoid receptor in rat hepatoma cells. Beck, G; Chasserot-Golaz, S; Corcos, L; Venetianer, A, 1990)	2.12
"Phenobarbital is a potent inducer of hepatic cytochrome P-450 and is a tumor promoter in the two-stage model of liver carcinogenesis. "	( Activation of liver macrophages following phenobarbital treatment of rats. Laskin, DL; Laskin, JD; Pilaro, AM; Robertson, FM, )	1.84
"Phenobarbital (PB) is known to be a promoter of liver tumorigenesis in rats and mice. "	( Effect of dietary phenobarbital on spontaneous hepatic tumorigenesis in germfree C3H/He male mice. Mitsuoka, T; Mizutani, T, 1988)	2.05
"Phenobarbital is a more strong and selective inductor of this form of cytochrome P-450 than 3-methylcholanthrene."	( [Determination of phenathrene-9,10-epoxidase in the liver microsomes of rats. The effect of induction on the activity of the enzyme]. Saprin, AN; Serdiuk, OA; Sotnichenko, AI; Sukhanov, VA, 1986)	0.99
"Phenobarbital was shown to be an effective quenching agent owing to the interaction with cytochrome P-450, a terminal luciferase component."	( [Action of phenobarbital on bacterial luciferase of Photobacterium fischeri]. Danilov, VS, )	1.24

Effects

Phenobarbital (PB) has a reputation for safety, and it is commonly believed that PB-related increases in serum aminotransferase levels do not indicate or predict the development of significant chronic liver disease. PhenobarBital has a high potential to elicit adverse reactions including severe skin eruptions and systemic involvements among the worldwide-prescribed drugs.

Phenobarbital has a high potential to elicit adverse reactions including severe skin eruptions and systemic involvements. It has been used in anticonvulsant concentrations in premature newborns in attempts to prevent periventricular and intraventricular hemorrhages.

Excerpt	Reference	Relevance
"Phenobarbital has a strong antiseizure effect with remarkably little sedation."	( Phenobarbital in Status epilepticus - Rediscovery of an effective drug. Trinka, E, 2023)	3.07
"Phenobarbital has a long elimination half-life and for this reason it is advisable to use means to accelerate clearance until the clinical condition of the patient shows improvement."	( [Accelerated elimination using hemoperfusion in a patient with phenobarbital intoxication]. Bouma, AW; Meynaar, IA; Peltenburg, HG; van Dam, B; Walenbergh-van Veen, MC, 2004)	1.28
"Phenobarbital (PB) has a reputation for safety, and it is commonly believed that PB-related increases in serum aminotransferase levels do not indicate or predict the development of significant chronic liver disease. "	( Hepatonecrosis and cholangitis related to long-term phenobarbital therapy: an autopsy report of two patients. Di Mizio, G; Gambardella, A; Labate, A; Perna, A; Quattrone, A; Ricci, P, 2007)	2.03
"As phenobarbital also has a hepatotrophic effect, its role in liver regeneration following partial hepatectomy (HTX) is not elucidated."	( Phenobarbital in comparison with carbon tetrachloride and phenobarbital-induced cirrhosis in rat liver regeneration. Hashimoto, M; Kothary, PC; Raper, SE, 1999)	2.26
"Phenobarbital has a high potential to elicit adverse reactions including severe skin eruptions and systemic involvements among the worldwide-prescribed drugs. "	( Characterization of drug-specific T cells in phenobarbital-induced eruption. Hashizume, H; Takigawa, M; Tokura, Y, 2002)	2.02
"Phenobarbital has a brief stimulating action."	( [Extent and duration of drug-induced stimulation of renal excretion of p-aminohippuric acid]. Bräunlich, H; Storch, R, 1976)	0.98
"Phenobarbital has been successfully used in the emergency department (ED) to manage symptoms of alcohol withdrawal, but few studies have reported outcomes for ED patients who receive phenobarbital and are discharged. "	( Return Encounters in Emergency Department Patients Treated with Phenobarbital Versus Benzodiazepines for Alcohol Withdrawal. Lebin, JA; Mudan, A; Murphy, CE; Smollin, CG; Wang, RC, 2022)	2.4
"Phenobarbital has fallen out of favor in many countries across Europe because of reports of hypotension, arrhythmias, and hypopnea."	( Phenobarbital in Status epilepticus - Rediscovery of an effective drug. Trinka, E, 2023)	3.07
"Phenobarbital (PB) has been acknowledged among clinicians as a potential alternative to benzodiazepines (BZD) to decrease the need for hospital length of stay and complications associated with alcohol withdrawal syndrome (AWS). "	( Current evidence and clinical utility of phenobarbital for alcohol withdrawal syndrome. Choi, H; Colgan, B; Kistler, H; Mercado, F; Nishimura, Y, 2023)	2.62
"Phenobarbital has been the most frequently prescribed drugs and thirteen percent of patients were in the escalation phase of treatment."	( The treatment outcomes of epilepsy and its root causes in children attending at the University of Gondar teaching hospital: A retrospective cohort study, 2018. Ayalew, AF; Beyene, A; Birhan, T; Mulat, G; Simachew Kassa, A, 2020)	1.28
"Phenobarbital (PB) has been shown to alter liver DNA methylation and hydroxymethylation patterns in mice in a time dependent manner."	( Reduced hepatic global hydroxymethylation in mice treated with non-genotoxic carcinogens is transiently reversible with a methyl supplemented diet. Buck, WR; Fossey, S; Liguori, MJ; Sharapova, T; Talaty, N; Van Vleet, TR, 2021)	1.34
"Phenobarbital has similar pharmacokinetics to select benzodiazepines frequently used for alcohol withdrawal."	( Benzodiazepines vs barbiturates for alcohol withdrawal: Analysis of 3 different treatment protocols. Kaucher, KA; Kehoe, J; Mintzer, D; Nelson, AC; Sankoff, J; Taub, J, 2019)	1.24
"Phenobarbital (PB) has been traditionally used as the first-line treatment for neonatal seizures. "	( Short-Term Neurodevelopmental Outcome in Term Neonates Treated with Phenobarbital versus Levetiracetam: A Single-Center Experience. Barbagallo, M; Corsello, G; Falsaperla, R; Mauceri, L; Pavone, P; Pisani, F; Ruggieri, M; Vitaliti, G, 2019)	2.19
"Phenobarbital has been shown to be an effective adjunctive therapy for AWS, reducing benzodiazepine use, in the emergency department."	( Phenobarbital and symptom-triggered lorazepam versus lorazepam alone for severe alcohol withdrawal in the intensive care unit. Lam, SW; Nguyen, TA, 2020)	2.72
"Phenobarbital has the advantage of low cost and simplicity."	( High-dose phenobarbital or erythropoietin for the treatment of perinatal asphyxia in term newborns. Avasiloaiei, A; Dimitriu, C; Moscalu, M; Paduraru, L; Stamatin, M, 2013)	1.51
"Phenobarbital has been suggested as a safe treatment that stabilises blood pressure and may protect against free radicals."	( Postnatal phenobarbital for the prevention of intraventricular haemorrhage in preterm infants. Odd, D; Smit, E; Whitelaw, A, 2013)	1.51
"Phenobarbital has been in use for a century. "	( Phenobarbitone in modern India. Gursahani, R, 2013)	1.83
"Phenobarbital monotherapy has been reported to reduce/eradicate seizure activity in 60-93 per cent of idiopathic epileptic dogs (IEDs)."	( Phenobarbital administration every eight hours: improvement of seizure management in idiopathic epileptic dogs with decreased phenobarbital elimination half-life. Barnett, CR; De Risio, L; Stabile, F, 2017)	2.62
"Phenobarbital has been in clinical use as an antiepileptic drug (AED) since 1912. "	( How did phenobarbital's chemical structure affect the development of subsequent antiepileptic drugs (AEDs)? Bialer, M, 2012)	2.26
"Phenobarbital has a long elimination half-life and for this reason it is advisable to use means to accelerate clearance until the clinical condition of the patient shows improvement."	( [Accelerated elimination using hemoperfusion in a patient with phenobarbital intoxication]. Bouma, AW; Meynaar, IA; Peltenburg, HG; van Dam, B; Walenbergh-van Veen, MC, 2004)	1.28
"Phenobarbital has been used in experimental models because it is an important agent of carcinogenesis promotion in the liver of rats, and it is also non-genotoxic, organ-specific and dose-dependent."	( [Potentially pre-neoplasics areas in rat's liver associated to chronic use of phenobarbital]. Hartmann, AA; Silva, HT, )	1.8
"Phenobarbital (PB) has a reputation for safety, and it is commonly believed that PB-related increases in serum aminotransferase levels do not indicate or predict the development of significant chronic liver disease. "	( Hepatonecrosis and cholangitis related to long-term phenobarbital therapy: an autopsy report of two patients. Di Mizio, G; Gambardella, A; Labate, A; Perna, A; Quattrone, A; Ricci, P, 2007)	2.03
"Phenobarbital has been suggested as a safe treatment that stabilises blood pressure and may protect against free radicals."	( Postnatal phenobarbital for the prevention of intraventricular hemorrhage in preterm infants. Odd, D; Whitelaw, A, 2007)	1.46
"Phenobarbital (PB) has been used at several pediatric centers for prophylaxis against neonatal hyperbilirubinemia. "	( Phenobarbital prophylaxis for hyperbilirubinemia in preterm infants. A controlled study of bilirubin disappearance and infant behavior. Boréus, LO; Wallin, A, 1984)	3.15
"Phenobarbital has been shown to offer effective prophylaxis against childhood febrile convulsions. "	( Sodium valproate versus phenobarbital in the prophylactic treatment of febrile convulsions in childhood. Lee, K; Melchior, JC, 1981)	2.01
"Phenobarbital pretreatment has no effect at all on either P1-450 mRNA or P2-450 mRNA."	( Characterization of cytochrome P2-450 (20-S) mRNA. Association with the P1-450 genomic gene and differential response to the inducers 3-methylcholanthrene and isosafrole. Altieri, M; Chen, YT; Ikeda, T; Nakamura, M; Nebert, DW; Negishi, M; Tukey, RH, 1983)	0.99
"Phenobarbital has been postulated to impair hepatic conversion of vitamin D to 25-hydroxyvitamin D [25(OH)D] either by accelerating the conversion of vitamin D to biologically inactive products or by directly inhibiting 25(OH)D production. "	( Effect of phenobarbital treatment on metabolism of vitamin D by rat liver. Baran, DT, 1983)	2.11
"Phenobarbital has no effect on the bacterial growth; however, it increases the content of luciferase in the culture."	( [Effect of phenobarbital on the luminescence system of luminous bacteria]. Mezhevikin, VV; Vysotskiĭ, ES; Zavoruev, VV, )	1.24
"Phenobarbital sodium (PhS) has been used in anticonvulsant concentrations in premature newborns in attempts to prevent peri- and intraventricular hemorrhages (PIVH). "	( Phenobarbital and cerebral blood flow during hypotension in newborn pigs. Contant, CF; Goddard-Finegold, J; Martin, CG; Michael, LH; Yamashita, Y, 1993)	3.17
"Phenobarbital has been used to increase enzyme conjugation of bilirubin."	( The use of jejunal transplants to treat a genetic enzyme deficiency. Burgos, AA; Jaffe, BM; Martinez-Noack, M, 1996)	1.02
"Phenobarbital treatment has been observed to be negatively associated with bladder cancer risk in a few studies. "	( Barbiturates, smoking, and bladder cancer risk. Bull, SA; Friedman, GD; Habel, LA, 1998)	1.74
"As phenobarbital also has a hepatotrophic effect, its role in liver regeneration following partial hepatectomy (HTX) is not elucidated."	( Phenobarbital in comparison with carbon tetrachloride and phenobarbital-induced cirrhosis in rat liver regeneration. Hashimoto, M; Kothary, PC; Raper, SE, 1999)	2.26
"Phenobarbital (PB) has long been known as an inducer of drug-metabolizing enzymes in liver, but the molecular mechanism underlying this induction is still poorly understood. "	( Regulation of phenobarbital induction of the cytochrome P450 2b9/10 genes in primary mouse hepatocyte culture. Involvement of calcium- and cAMP-dependent pathways. Corcos, L; Fautrel, A; Galisteo, M; Guillouzo, A; Joannard, F; Lagadic-Gossmann, D; Marc, N, 2000)	2.11
"Phenobarbital has long been used as a sedative and antiepileptic drug. "	( Gene induction by Phenobarbital: an update on an old question that receives key novel answers. Corcos, L; Lagadic-Gossmann, D, 2001)	2.09
"Phenobarbital has a high potential to elicit adverse reactions including severe skin eruptions and systemic involvements among the worldwide-prescribed drugs. "	( Characterization of drug-specific T cells in phenobarbital-induced eruption. Hashizume, H; Takigawa, M; Tokura, Y, 2002)	2.02
"Phenobarbital alone has been useful, so far, in the treatment of cholesterol gallstones."	( Barbituates and biliary function. Capron, JP; Erlinger, S, 1975)	0.98
"Phenobarbital has shown to increase both the content of rat liver microsomal proteins and the specific activity of those."	( [Study of metabolic activation of chemical compounds by using microorganisms. I. Effect of inducers of microsomal systems]. Abilev, SK; Akin'shina, LP; Fonshtein, LM, 1978)	0.98
"Phenobarbital has been observed clinically to alter the metabolism of meperidine, with resultant enhanced toxicity. "	( The effect of phenobarbital on the metabolism of meperidine in normal volunteers. Schwartz, I; Stambaugh, JE; Wainer, IW, 1978)	2.06
"Phenobarbital has a brief stimulating action."	( [Extent and duration of drug-induced stimulation of renal excretion of p-aminohippuric acid]. Bräunlich, H; Storch, R, 1976)	0.98
"Phenobarbital sodium has been used in anticonvulsant concentrations (15 to 40 micrograms/mL serum) in premature newborns in attempts to prevent periventricular and intraventricular hemorrhages. "	( Phenobarbital and cerebral blood flow during hypertension in the newborn beagle. Adham, BI; Donley, DK; Goddard-Finegold, J; Michael, LH, 1990)	3.16
"Phenobarbital sodium has been given to premature infants in anticonvulsant dosages in attempts to prevent hemorrhages, but its efficacy in clinical studies has been disputed."	( Reduction in incidence of periventricular, intraventricular hemorrhages in hypertensive newborn beagles pretreated with phenobarbital. Armstrong, DL; Goddard-Finegold, J, 1987)	1.2
"Phenobarbital, which has been reported to exhibit all these changes mentioned, is a weaker inducer of delta-aminolaevulinate synthetase and increases the rate of haem synthesis only after a considerable time-lag in fed female rats, when compared with the effects observed with allylisopropylacetamide."	( Biochemical effects of the porphyrinogenic drug allylisopropylacetamide. A comparative study with phenobarbital. Padmanaban, G; Rao, MR, 1973)	1.19

Actions

Phenobarbital was chosen because its value had been demonstrated as a marker of compliance in long-course therapies. Any significant departure from steady-state concentrations (achieved with full compliance) indicating one or more missed doses. Phenobarbitals may cause hyperactivity, behavioral problems, sedation, and even dementia.

Excerpt	Reference	Relevance
"Phenobarbital was used because of non-pharmacological treatment failure."	( Neonatal abstinence syndrome due to prenatally citalopram exposure: A case report. Bas, AY; Celik, IH; Demirel, N; Erol, S; Ozcan, B, 2017)	1.18
"Phenobarbital is able to enhance the yield of epoxidation to give preferentially diepoxide (1R, 2S, 4R, 7R)-trans-10b."	( Stereochemical aspects in the 4-vinylcyclohexene biotransformation with rat liver microsomes and purified cytochrome P450s: diepoxide formation and hydrolysis. Amato, G; Chiappe, C; De Rubertis, A; Gervasi, PG; Piegari, G, 2003)	1.04
"Phenobarbital is known to increase rabbit but not rat renal mixed-function oxidase activities; however, several other compounds such as polybrominated biphenyls (PBB), trans-stilbene oxide (TSO) and beta-naphthoflavone (BNF) have been shown to induce renal enzyme activities in rats."	( Effects of drug-metabolizing enzyme inducers on cephaloridine toxicity in Fischer 344 rats. Hook, JB; Kuo, CH, 1982)	0.99
"Phenobarbital alone did not produce any apparent amount of foci in liver."	( The effect of pre- and post-treatment with phenobarbital on the extent of gamma-glutamyl transpeptidase positive foci induced in rat liver by N-nitrosomorpholine. Bannasch, P; Kunz, W; Schwarz, M, 1983)	1.25
"Phenobarbital may cause hyperactivity, behavioral problems, sedation, and even dementia; these effects are dose related to some extent."	( Side effects of phenobarbital and phenytoin during long-term treatment of epilepsy. Iivanainen, M; Savolainen, H, 1983)	1.33
"The phenobarbital-mediated increase in hepatic triacylglycerol content could not be explained by a decrease in the hepatic triacylglycerol secretion rate as measured by the Triton WR1339 technique."	( Triacylglycerol metabolism in the phenobarbital-treated rat. Goldberg, DM; Roncari, DA; Roomi, MW; Yu, A, 1981)	1.02
"Phenobarbital was chosen because its value had been demonstrated as a marker of compliance in long-course therapies, any significant departure from steady-state concentrations (achieved with full compliance) indicating one or more missed doses."	( Initial evaluation of low-dose phenobarbital as an indicator of compliance with antimalarial drug treatment. Feely, M; Fungladda, W; Hay, A; Karbwang, J; Pickard, CE; Shires, S, 1998)	1.31
"Phenobarbital-type inducers increase the ALDH1A3, while polycyclic hydrocarbons (such as BaP and TCDD) increase the expression of the two members of ALDH3A subfamily (3A1 and 3A2)."	( Phenobarbital inducibility and differences in protein expression of an animal model. Karamanakos, P; Marselos, M; Pappas, P; Stephanou, P; Vasiliou, V, 2001)	2.47
"Phenobarbital plays a role in the cytoprotection of hepatocytes to itraconazole-induced but not fluconazole-induced cytotoxicity in vitro."	( Itraconazole- and fluconazole-induced toxicity in rat hepatocytes: a comparative in vitro study. Hassim, SM; Samsudin, SH; Somchit, N, 2002)	1.04
"Phenobarbital tends to lower the plasma phenytoin level when the two drugs are used simultaneously."	( In vivo interaction of anticonvulsant drugs. The mathematical correlation of plasma levels of anticonvulsant drugs in epileptic patients. Abarbanel, J; Eylath, U; Herishanu, Y; Rosenberg, P, 1978)	0.98
"Phenobarbital has shown to increase both the content of rat liver microsomal proteins and the specific activity of those."	( [Study of metabolic activation of chemical compounds by using microorganisms. I. Effect of inducers of microsomal systems]. Abilev, SK; Akin'shina, LP; Fonshtein, LM, 1978)	0.98
"Phenobarbital, however, did cause a reduction in bile acid synthesis measured by 14CO2 evolution and by biliary bile acid excretion."	( Measurement of bile acid synthesis by 14CO2: the metabolism of propionyl CoA. Davis, RA; Kern, F; Showalter, P, 1975)	0.98
"Phenobarbital was shown to lower the toxicity of DDT, norethandrolone had the opposite effect, and 3-methylcholanthrene was without any significant effect."	( [The effect of pretreatment with enzyme inducers on the acute toxicity of DDT (1, 1-bis-(p-chlorophenyl)-2,2,2-trichloroethane) in rats]. Brodeur, J; Lambert, G, 1975)	0.98
"The phenobarbital-induced increase in ileal absorption of bile acids might be responsible for the increase in pool size and biliary bile acid excretion."	( Effects of ethinyl estradiol and phenobarbital on bile acid synthesis and biliary bile acid and cholesterol excretion. Davis, RA; Kern, F, 1976)	0.99
"Phenobarbital did not cause peroxisome proliferation and inhibited the corresponding clofibrate-dependent proliferation."	( Influence of single and concurrent clofibrate and phenobarbital administration on cytochrome P450-dependent mixed function oxidase activities and peroxisome proliferation in male rat liver. Close, I; Gibson, GG; Goldfarb, PS; Howes, D; Shackleton, G; Sharma, R, 1992)	1.26
"Phenobarbital tended to increase the biliary excretion of AA-GS, but not in a statistically significant manner."	( Biliary excretion of acetaminophen-glutathione as an index of toxic activation of acetaminophen: effect of chemicals that alter acetaminophen hepatotoxicity. Gregus, Z; Klaassen, CD; Madhu, C, 1989)	1
"Phenobarbital (PB) promotes hepatic tumorigenesis when chronically administered to male B6C3F1 mice after initiation with diethylnitrosamine (DENA) at 30 days of age. "	( Phenobarbital promotion in diethylnitrosamine-initiated infant B6C3F1 mice: influence of gender. Klaunig, JE; Weghorst, CM, 1989)	3.16
"A phenobarbital-mediated increase in enzyme protein and a concomitant enhancement of the corresponding mRNA was seen in hepatocytes of the centrilobular areas of the liver acinus."	( Phenobarbital induction of cytochrome P-450 in normal and preneoplastic rat liver: comparison of enzyme and mRNA expression as detected by immunohistochemistry and in situ hybridization. Buchmann, A; Friedberg, T; Kunz, W; Peres, G; Schwarz, M; Waxman, DJ, 1987)	2.27
"The phenobarbital-induced increase in Km and the decreases in benzo[a]pyrene hydroxylation were not observed in rats fed 0.5% menhaden oil or a diet devoid of fat."	( Phenobarbital depression of hepatic microsomal benzo[a]pyrene hydroxylation in rats starved and refed a diet containing menhaden fish oil: substrate and fat level dependency. Dharwadkar, SM; Wade, AE, 1987)	2.2
"Phenobarbital appears to produce similar behavioral effects on mice and humans with excitation at low and sedation or depression at higher doses. "	( Phenobarbital during pregnancy in mouse and man. Middaugh, LD, 1986)	3.16
"The phenobarbital-induced increase in the phospholipid and cytochrome P-450 content of the microsomes, as well as in the activities of microsomal reduced nicotinamide-adenine dinucleotide phosphate-cytochrome c reductase and N-demethylase, was correlated with the morphometric data on the endoplasmic reticulum."	( Correlated morphometric and biochemical studies on the liver cell. II. Effects of phenobarbital on rat hepatocytes. Hess, R; Stäubli, W; Weibel, ER, 1969)	0.95

Treatment

Phenobarbital treatment (50 mg/kg) resulted in a significant decrease of proliferative capacity in the dentate gyrus. In phenobarbina-treated dogs, significantly increased levels of alkaline phosphatase, gamma-glutamyl-transferase and other liver enzymes.

Excerpt	Reference	Relevance
"Phenobarbital treated mice showed damped corticosterone levels and a less stable 24 hours activity rhythm as well as an increase in activity during the light phase, reminiscent of sleep disruption."	( Relationship between locomotor activity rhythm and corticosterone levels during HCC development, progression, and treatment in a mouse model. Ali, AAH; Hassan, SA; Jänicke, RU; Korf, HW; Pfeffer, M; Sohn, D; von Gall, C; Yassine, M, 2021)	1.34
"Phenobarbital treatment (50 mg/kg) resulted in a significant decrease of proliferative capacity in the dentate gyrus."	( Caffeine Protects Against Anticonvulsant-Induced Impaired Neurogenesis in the Developing Rat Brain. Bührer, C; Endesfelder, S; Schiller, C; von Haefen, C; Weichelt, U; Winter, K, 2018)	1.2
"In phenobarbital-treated dogs, significantly increased levels of alkaline phosphatase, gamma-glutamyl-transferase and other liver enzymes occurred, while no such effect was observed in the imepitoin group."	( Clinical efficacy and safety of imepitoin in comparison with phenobarbital for the control of idiopathic epilepsy in dogs. de Vries, F; Keefe, TJ; Löscher, W; Rundfeldt, C; Tipold, A, 2015)	1.17
"Phenobarbital treatment greatly increased nuclear CAR accumulation in the livers of KO males as compared to those of wild type (WT) males."	( The roles of co-chaperone CCRP/DNAJC7 in Cyp2b10 gene activation and steatosis development in mouse livers. Kanayama, T; Moore, R; Negishi, M; Ohno, M; Ray, M, 2014)	1.12
"Five phenobarbital treated dogs were classified as true responders (≥50% reduction in seizures/month) whereas none of the levetiracetam treated dogs fulfilled this criterion."	( A single-blinded phenobarbital-controlled trial of levetiracetam as mono-therapy in dogs with newly diagnosed epilepsy. Berendt, M; Fredsø, N; Møller, A; Sabers, A; Toft, N, 2016)	1.23
"Phenobarbital treatment was associated with decreased mortality, which might be confounded by somatic comorbidity among patients receiving chlordiazepoxide."	( Phenobarbital compared to benzodiazepines in alcohol withdrawal treatment: A register-based cohort study of subsequent benzodiazepine use, alcohol recidivism and mortality. Askgaard, G; Fink-Jensen, A; Hallas, J; Madsen, KG; Molander, AC; Pottegård, A, 2016)	2.6
"Phenobarbital treatment caused a significant decrease in triiodothyronine and free thyroxine concentrations (17% and 40%, respectively) in the sensitive C3H/He mice by the end of 60-day treatment, while in the resistant mice, these changes were not observed."	( The increased CAR-dependent metabolism of thyroid hormones in mice with high cancer susceptibility. Kaledin, V; Merkulova, T; Obut, T; Pakharukova, M; Smetanina, M, 2010)	1.08
"Phenobarbital treatment resulted in eradication of seizures (17/20 [85%]) significantly more often than did bromide (12/23 [52%]); phenobarbital treatment also resulted in a greater percentage decrease in seizure duration (88 ± 34%), compared with bromide (49 ± 75%). "	( Comparison of phenobarbital with bromide as a first-choice antiepileptic drug for treatment of epilepsy in dogs. Boothe, DM; Carpenter, DM; Dewey, C, 2012)	2.18
"Phenobarbital treatment caused significant induction of hepatic RED, APD, AHH, GST and QR activities."	( Influence of phenobarbital and carbon tetrachloride on the modulation of tissue retention profile of hexachlorocyclohexane in rats. Anand, M; Das, M; Khanna, RN, 2002)	1.41
"Phenobarbital treatment sharply increased HO-1 mRNA and protein expression in selenium-deficient liver and HO activity in hepatocytes, but had no effect in control liver or in the Kupffer cell/endothelial cell fraction of selenium-deficient liver."	( Selective induction of liver parenchymal cell heme oxygenase-1 in selenium-deficient rats. Burk, RF; Ferris, CD; Hill, KE; Mostert, V, 2003)	1.04
"Phenobarbital pretreatment (80 mg/kg/d for 4 d) in VPA-treated rats increased plasma and liver levels of free 15-F(2t)-IsoP by 5-fold and 3-fold, respectively, when compared to control groups."	( The effect of valproic acid on hepatic and plasma levels of 15-F2t-isoprostane in rats. Abbott, FS; Chang, TK; Chen, J; Tong, V, 2003)	1.04
"Phenobarbital treatment resulted in increases in total cytochromes P450 and metabolism of three resorufin analogues, but not CYP6L1 nor CYP9E2 mRNA."	( Induction of P450 monooxygenases in the German cockroach, Blattella germanica L. Brown, D; Scott, JG; Wen, Z; Zhang, L, 2003)	1.04
"Phenobarbital (PB) treatment impairs the biliary excretion of some organic anions. "	( Phenobarbital alters hepatic Mrp2 function by direct and indirect interactions. Brouwer, KL; Han, YH; Jansen, PL; Meier, PJ; Patel, NJ; Stieger, B; Zamek-Gliszczynski, MJ; Zhang, P, 2003)	3.2
"In phenobarbital-treated dogs with high serum total AP activity in the cross-sectional study, the increase was due predominantly to increased activities of the corticosteroid-induced (C-AP) and liver (L-AP) isoenzymes. "	( Serum alkaline phosphatase isoenzyme profiles in phenobarbital-treated epileptic dogs. Cribb, AE; Gaskill, CL; Hoffmann, WE, 2004)	1.2
"Phenobarbital treatment was associated with increased C-AP and L-AP isoenzyme activities and with a minor increase in B-AP activity. "	( Serum alkaline phosphatase isoenzyme profiles in phenobarbital-treated epileptic dogs. Cribb, AE; Gaskill, CL; Hoffmann, WE, 2004)	2.02
"Phenobarbital treatment did not change the CAR expression profiles and did not induce in either rats and rabbits the pulmonary CYP 2B isoforms, as judged by western blot analysis and the marker pentoxyresorufin O-dealkylase and 7-ethoxy-4-trifluoroethylcoumarin O-deethylase activities."	( CAR and PXR expression and inducibility of CYP2B and CYP3A activities in rat and rabbit lungs. Chirulli, V; Fiorio, R; Gervasi, PG; Longo, V; Marini, S; Mazzaccaro, A, 2005)	1.05
"3. Phenobarbital treatment resulted in a significant, 56%, decrease (P=0.04) in the maximum nicotine plasma concentration and a 46% decrease (P=0.003) in the area under the concentration-time curve."	( Phenobarbital increases monkey in vivo nicotine disposition and induces liver and brain CYP2B6 protein. Lee, AM; Miksys, S; Tyndale, RF, 2006)	2.29
"Phenobarbital pretreatment increased methoxyflurane nephrotoxicity in vivo (increased diuresis and blood urea nitrogen and decreased urine osmolality) and induced in vitro hepatic microsomal methoxyflurane metabolism to inorganic fluoride (2-fold), dichloroacetatic acid (1.5-fold), and MDFA (5-fold). "	( New insights into the mechanism of methoxyflurane nephrotoxicity and implications for anesthetic development (part 1): Identification of the nephrotoxic metabolic pathway. Kharasch, ED; Liggitt, HD; Park, SB; Schroeder, JL; Sheffels, P; Whittington, D, 2006)	1.78
"In phenobarbital-treated patients, serum levels in 73% of the patients were in therapeutic range of 10-40 microg/ml, and about 44% of phenytoin-treated patients had serum levels in therapeutic range of 10-20 microg/ml."	( Evaluation of therapeutic drug level monitoring of phenobarbital, phenytoin and carbamazepine in Iranian epileptic patients. Babaei, A; Eslamai, MH, 2007)	1.11
"Phenobarbital treatment for two weeks was associated with a significant decrease in serum thyroxine (T4) level and in the free thyroxine index (T3U x T4) of 18% and 16%, respectively."	( Changes in thyroid function tests during phenobarbital treatment in late pregnancy. Heikkinen, JE; Luoma, PV; Ylöstalo, PR, )	1.12
"The phenobarbital-treated guinea pigs manifested increased hepatic triacylglycerol content and serum triacylglycerol concentration, accompanied by enhanced ability of cell-free fractions of liver to synthesize glycerolipids in vitro from sn-[14C]glycerol 3-phosphate and fatty acids."	( Effects of phenobarbital upon triacylglycerol metabolism in the guinea pig. Goldberg, DM; Roncari, DA; Roomi, MW; Yu, A, 1981)	1.13
"Phenobarbital pretreatment primarily induced 2- and 3-hydroxylation, the latter most dramatically."	( Biphenyl metabolism by rat liver microsomes: regioselective effects of inducers, inhibitors, and solvents. Haugen, DA, )	0.85
"Phenobarbital treatment increased N- and C-hydroxylation, whereas 3-methylcholanthrene treatment had an inhibitory effect on both pathways."	( The metabolism of (R)-(-)-amphetamine by rabbit liver microsomes. Initial products. Cho, AK; Di Stefano, EW; Florence, VM; Sum, CY, )	0.85
"Phenobarbital treatment shortened the time course of beta blockade."	( Interaction of phenobarbital with propranolol in the dog. 3. Beta blockade. Abramson, FP; Bai, SA, 1983)	1.34
"Phenobarbital treatment resulted in significant increases in serum GGT activity (p less than 0.05) and urinary d-glucaric acid excretion (p less than 0.005)."	( Effects of phenobarbital on unconjugated bilirubin clearance, gamma-glutamyltranspeptidase and urinary d-glucaric acid in patients with Gilbert's syndrome. Hirayama, C; Kawasaki, H; Kimura, N; Murawaki, Y, 1982)	1.38
"Phenobarbital treatment prior to administration of AFB1 decreased adduct formation in most groups, and abolished differences in adduct formation due to diet."	( Effects of dietary selenium and vitamin E on covalent binding of aflatoxin to chick liver cell macromolecules. Campbell, TC; Chen, J; Combs, GF; Goetchius, MP, 1982)	0.99
"Phenobarbital treatment increased the rate of RNA synthesis 10-fold over that observed for hepatocytes from untreated rats."	( The effect of phenobarbital on the transcriptional activity of liver. Hardwick, JP; Richardson, A; Schwalm, F, 1983)	1.35
"Phenobarbital treatment and streptozotocin-diabetes both increase, in mouse and rat microsomes, a benzphetamine-N-demethylase activity which can be inhibited by a specific antibody raised against purified rat phenobarbital-induced cytochrome P-450. "	( Study of benzphetamine-N-demethylase in streptozotocin-diabetic mice and rats: evidence for the induction of catalytically and immunologically specific forms of cytochrome P450. Le Provost, E; Leroux, JP; Rouer, E, )	1.57
"Phenobarbital treatment resulted in a 3.2-fold increase in glutathione S-transferase mRNA over levels found in control rats, while trans-stilbene oxide increased glutathione S-transferase mRNA levels 5.7-fold."	( Rat glutathione S-transferase. Cloning of double-stranded cDNA and induction of its mRNA. Kalinyak, JE; Taylor, JM, 1982)	0.99
"The phenobarbital-treated infants who bled, however, were also significantly larger and more mature than control infants who bled."	( Effect of prophylactic phenobarbital on intraventricular hemorrhage in high-risk infants. Bedard, MP; Dayal, B; Pantoja, A; Poland, RL; Shankaran, S; Slovis, TL, 1984)	1.06
"Phenobarbital (PB) treatment did not alter any of these enzyme activities."	( Immunochemical detection and quantitation of microsomal cytochrome P-450 and reduced nicotinamide adenine dinucleotide phosphate:cytochrome P-450 reductase in the rat ventral prostate. Glaumann, H; Gustafsson, JA; Haaparanta, T; Halpert, J, 1983)	0.99
"Phenobarbital + DBBD treatment gave results which did not differ significantly from those obtained with phenobarbital alone."	( 2,2-Dimethyl-5-t-butyl-1,3-benzodioxole: an unusual inducer of microsomal enzymes. Cook, JC; Hodgson, E, 1984)	0.99
"Phenobarbital pretreatment did not change the ETU-induced maternal or fetal effects."	( Ethylenethiourea-induced hindpaw deformities in mice and effects of metabolic modifiers on their occurrence. Khera, KS, 1984)	0.99
"Phenobarbital pretreatment markedly increased the metabolism of felodipine and its pyridine analogue."	( Cytochrome P-450-dependent oxidation of felodipine--a 1,4-dihydropyridine--to the corresponding pyridine. Bäärnhielm, C; Borg, KO; Skånberg, I, 1984)	0.99
"In phenobarbital-treated rat hepatocytes, filipin-sterol complexes in the lysosomes or microbodies were distributed unevenly."	( Distribution of filipin-sterol complexes in rat hepatocytes. Murakoshi, M; Osamura, Y; Satoh, S; Watanabe, K, 1984)	0.78
"Both phenobarbital pretreatment and SKF525A treatment altered to anticoagulant response to brodifacoum."	( Dispositional and pharmacodynamic characteristics of brodifacoum in warfarin-sensitive rats. Bachmann, KA; Sullivan, TJ, 1983)	0.72
"Phenobarbital (PB) treatment of rats of various strains leads to the accumulation of liver mRNAs which encode two or three immunochemically related but electrophoretically separable cytochrome P-450 polypeptides. "	( Cloned cytochrome P-450 cDNA. Nucleotide sequence and homology to multiple phenobarbital-induced mRNA species. Adesnik, M; Kumar, A; Raphael, C, 1983)	1.94
"Phenobarbital pretreatment also potentiated in vitro 14CHCl3 metabolism to 14CO2 and covalently bound radioactivity in rabbit renal cortical slices and microsomes."	( Mechanism of chloroform nephrotoxicity. IV. Phenobarbital potentiation of in vitro chloroform metabolism and toxicity in rabbit kidneys. Bailie, MB; Hook, JB; Newton, JF; Smith, JH, 1984)	1.25
"Phenobarbital treatment was associated with a uniform shift to a higher intensity light scatter (relative increase in cell size) within each of the four selected regions."	( A comparison of hepatocyte size distribution in untreated and phenobarbital-treated rats as assessed by flow cytometry. Muller-Eberhard, U; Willson, RA; Wormsley, SB, 1984)	1.23
"In phenobarbital-treated rats, fluorescence was much more intense, with a similar but much greater difference between the centrilobular and perilobular zones."	( Immunofluorescence of phenobarbital inducible cytochrome P-450 in the hepatic lobule of normal and phenobarbital-treated rats. Mishima, A; Ohnishi, K; Okuda, K, )	0.96
"Phenobarbital pretreatment appears to be effective as an inducing agent for all the enzymes studied, but only after birth."	( Perinatal development of cytochrome P-450, NADPH-cytochrome c reductase and ethoxycoumarin deethylase in rat liver nuclear membranes. Assael, BM; Clos, V; Romano, M; Salmona, M, 1982)	0.99
"Phenobarbital treatment significantly increased the rate of methoxyflurane defluorination (673% of control), whereas the rates of sevoflurane defluorination (127% of control) and enflurane defluorination (86% of control) were not altered significantly."	( Metabolism by rat hepatic microsomes of fluorinated ether anesthetics following ethanol consumption. Dooley, JR; Mazze, RI; Rice, SA, 1983)	0.99
"Phenobarbital pretreatment reduced both the antitumor efficacy and toxicity of CCNU (factor of approximately 0.8), while SKF 525A increased the effect of CCNU in both cases (factor of approximately 1.6)."	( Effect of pretreatment with phenobarbital or SKF 525A on the toxicity and antitumor activity of lomustine. Siemann, DW, 1983)	1.28
"The phenobarbital treatment became unnecessary when neoplastic nodules were present."	( Promotion mechanism of phenobarbital and partial hepatectomy in DENA hepatocarcinogenesis cell kinetics effect. Barbason, H; Betz, EH; Rassenfosse, C, 1983)	1.06
"Phenobarbital pretreatment produced a significant increase in liver weight and decreased the sodium pentobarbital (75 mg/kg, i.p.) induced sleep-time to 41 min compared to 141 min in controls."	( Effect of pretreatment with sodium phenobarbital on the toxicity of soman in mice. Clement, JG, 1983)	1.26
"Phenobarbital treatment for a period from 5 to 12 months had no effect on the 25-OHD levels."	( Normal serum 25-hydroxyvitamin D levels in phenobarbital-treated toddlers. Camfield, CS; Camfield, PR; Delvin, EE; Glorieux, FH, 1983)	1.25
"Phenobarbital pretreatment has no effect at all on either P1-450 mRNA or P2-450 mRNA."	( Characterization of cytochrome P2-450 (20-S) mRNA. Association with the P1-450 genomic gene and differential response to the inducers 3-methylcholanthrene and isosafrole. Altieri, M; Chen, YT; Ikeda, T; Nakamura, M; Nebert, DW; Negishi, M; Tukey, RH, 1983)	0.99
"Phenobarbital pretreatment synergistically interacted with benzene exposure to further increase sister chromatid exchanges in female mice, induce greater inhibition of cellular proliferation in male mice, and induce a significant level of chromatid-type chromosomal aberrations in both sexes."	( Cytogenetic effects of inhaled benzene in murine bone marrow: induction of sister chromatid exchanges, chromosomal aberrations, and cellular proliferation inhibition in DBA/2 mice. Costa, DL; Drew, RT; Tice, RR, 1980)	0.98
"Phenobarbital (PB) pretreatment significantly increased phenol excretion in rats exposed to benzene at 800 mg m-3 and higher concentrations."	( Kinetics of benzene metabolism in rats in inhalation exposure. Frantík, E; Gut, I, 1980)	0.98
"Phenobarbital pretreatment increased the activation of cyclophosphamide to mutagenic metabolites by maternal liver microsomes 10-fold and liver cytochrome P-450 content 1.8 fold; however, this drug did not alter the activation of cyclophosphamide by maternal kidney, by placenta or by the fetus."	( Modification of the mutagenicity and teratogenicity of cyclophosphamide in rats with inducers of the cytochromes P-450. Hales, BF, 1981)	0.98
"In phenobarbital-pretreated mice there was a marked increase in the amount of ADR or DR aglycones in the liver, and a decrease in the levels of unchanged ADR or DR."	( Body residue and metabolism of adriamycin and daunorubicin in control and phenobarbital-pretreated mice. Bolanowska, W; Gessner, T, 1982)	1.01
"3. Phenobarbital treatment of rats caused an increase in the liver microsomal N-dealkylation of tiaramide in vitro, but had little effect on N-oxidation."	( Metabolism of tiaramide in vitro. I. Oxidative metabolism of tiaramide by human and rat liver microsomes. Iwasaki, K; Kamataki, T; Kato, R; Noguchi, H, 1982)	0.78
"Phenobarbital treatment increased both the total and intrinsic clearance of (S)-(-)-warfarin almost threefold but did not reduce the coefficient of variation of the intrinsic clearance."	( Comparative pharmacokinetics of coumarin anticoagulants. XLVI: Effect of treatment of phenobarbital on pharmacokinetics of (S)-(-)-warfarin in rats. Levy, G; Slattery, JT; Yacobi, A, 1980)	1.21
"Phenobarbital pretreatment of rats did not markedly affect rates of alpha-hydroxylation of NPYR or NNN."	( Assays for metabolic alpha-hydroxylation of N'-nitrosonornicotine and N-nitrosopyrrolidine and the influence of modifying factors. Chen, CB; Hecht, SS; Hoffmann, D; McCoy, GD, 1980)	0.98
"(c) Phenobarbital pretreatment induces no detectable P1-450 or P-448."	( Structural gene products of the murine Ah complex. Differences in ontogenesis and glucosamine incorporation between liver microsomal cytochromes P1-450 and P-448 induced by polycyclic aromatic compounds. Garcia, GS; Jensen, NM; Nebert, DW; Negishi, M, 1981)	0.74
"Phenobarbital pretreatment markedly enhances propynylic hydroxylation (C) but has little or no effect on the other metabolic pathways."	( Metabolism of N-(5-pyrrolidinopent-3-ynyl)-succinimide (BL 14) in rat liver preparations. Characterization of four oxidative reactions. Anderson, E; Hallström, G; Lindeke, B, 1981)	0.98
"Phenobarbital pretreatment of mice enhanced the metabolic reactions of the seven compounds, but did not elevate those of acrylamide and crotonamide."	( Studies on in vitro metabolism of acrylamide and related compounds. Hashimoto, K; Tanii, H, 1981)	0.98
"Phenobarbital treatment decreased blood levels only prior to reaching equilibrium and did not alter the response to epinephrine-induced cardiac arrhythmias."	( Effects of alterations in drug metabolism on chloroform-induced cardiac arrhythmias in rabbits. Carlson, GP, 1981)	0.98
"3. Phenobarbital treatment increased the hepatic content of triacylglycerol after 5 days in starved male and female rats, as well as in non-starved male rats; non-starved females were not tested in this regard."	( Triacylglycerol metabolism in the phenobarbital-treated rat. Goldberg, DM; Roncari, DA; Roomi, MW; Yu, A, 1981)	1.06
"Phenobarbital treatment significantly reduced the level of unconjugated serum bilirubin in patients with acute hepatitis or Gilbert's syndrome, but without any difference within these two groups of patients."	( Diagnosis of Gilbert's syndrome. Reliability of the caloric restriction and phenobarbital stimulation tests. Hardt, F; Juhl, E; Thomsen, HF, 1981)	1.21
"Phenobarbital treatment slightly decreased blood levels of methylchloroform and the incidence of cardiac arrhythmias."	( Effect of alterations in drug metabolism on epinephrine-induced cardiac arrhythmias in rabbits exposed to methylchloroform. Carlson, GP, 1981)	0.98
"Phenobarbital treatment produced an increase in relative liver weight accompanied by elevated activities of pulmonary aminopyrine N-demethylase and hepatic aniline hydroxylase and aminopyrine N-demethylase."	( Modification by phenobarbital of chlorphentermine-induced changes in lung morphology and drug-metabolizing enzymes in newborn rats. Kacew, S; Narbaitz, R; Parulekar, MR; Ruddick, JA; Villeneuve, DC, )	1.2
"In phenobarbital-treated rats disulfiram 100 mg/kg did not alter the induction response as indicated by the cytochrome P-450 content, but inhibited the p-nitroanisole activity to control levels."	( Effect of long-term disulfiram administration on rat liver. Andreasen, PB; Milandri, M; Poulsen, HE; Ranek, L, 1980)	0.78
"Phenobarbital treatment decreased the levels of induction by the halogenated benzenes."	( Various pharmacokinetic parameters in relation to enzyme-inducing abilities of 1,2,4-trichlorobenzene and 1,2,4-tribromobenzene. Carlson, GP; Smith, EN, 1980)	0.98
"Phenobarbital treatment is recommended in patients with congenital hemolytic anemia in whom hyperbilirubinemia is not improved by splenectomy or in whom splenectomy is not indicated."	( Successful long-term phenobarbital therapy of hyperbilirubinemia in congenital hemolytic anemia due to glucose phosphate isomerase deficiency. Schröter, W, 1980)	1.3
"Phenobarbital treatment decreased these affinity constants, which were similar for each activity measured."	( Hexobarbital-binding, hydroxylation and hexobarbital-dependent hydrogen peroxide production in hepatic microsomes of guinea pig, rat and rabbit. Heinemeyer, G; Hildebrandt, AG; Nigam, S, 1980)	0.98
"The phenobarbital treatment resulted in decreased content of free cholesterol in liver microsomes in a strain of rat that responded with increased cholesterol 7 alpha-hydroxylase activity."	( Stimulation of HMG-CoA reductase as a consequence of phenobarbital-induced primary stimulation of cholesterol 7 alpha-hydroxylase in rat liver. Björkhem, I; Eggertsen, G; Sudjana-Sugiaman, E, 1994)	1.02
"Phenobarbital treatment resulted in increases in P450 2B1/2 (7-pentoxyresorufin O-depentylase and 16 alpha- and 16 beta-hydroxylation of testosterone) activities, while minor effects were observed on P450 3A1 (testosterone 6 beta-hydroxylation) activity."	( Cytochrome P450 activities in pure and co-cultured rat hepatocytes. Effects of model inducers. Castell, JV; Donato, MT; Gómez-Lechón, MJ, 1994)	1.01
"Phenobarbital treatment increased the concentrations of cytochrome P-450 in both groups to the same extent."	( Effect of nutritional obesity on the induction of CYP2B enzymes following phenobarbital treatment. Bandyopadhyay, AM; Blouin, RA; Robertson, LW; Zannikos, PN, )	1.08
"Phenobarbital treatment had no significant effect on CBF 60 min after loading dosage (20 mg/kg i.v.)."	( The effect of phenobarbital on cerebral blood flow in newborn infants with foetal distress. Andersen, K; Ebbesen, F; Jensen, KA, 1994)	1.37
"Phenobarbital treatment increased the concentrations of total cytochrome P450 in both lean and obese rats to the same extent."	( Expression of the CYP3A and CYP2C11 enzymes in a nutritionally obese rodent model: response to phenobarbital treatment. Bandyopadhyay, AM; Blouin, RA; Robertson, LW; Zannikos, PN, 1994)	1.23
"Only phenobarbital pretreatment also significantly reduced GSH and ATP depletion."	( Influence of inducers and inhibitors of cytochrome P450 on the hepatotoxicity of hydrazine in vivo. Jenner, AM; Timbrell, JA, 1994)	0.74
"Phenobarbital treatment increased the levels of microsomal proteins recognized by antibody to cytochrome P4502B, as well as dealkylases of pentoxyresorufin, but decreased the level of proteins recognized by anti-cytochrome P450C11 or cytochrome P4502E."	( Presence of proteins recognized by mammalian cytochrome P-450 antibodies in Euglena gracilis. Beaune, P; Briand, J; de Waziers, I; Flinois, JP; Julistiono, H; Leroux, JP, 1993)	1.01
"Phenobarbital treatment increased the electrogenic transport of [35S]sulfobromophthalein (BSP) (5 and 50 microM) but not the electrogenic uptake of [14C] glycocholic acid (10 and 200 microM)."	( Selective induction by phenobarbital of the electrogenic transport of glutathione and organic anions in rat liver canalicular membrane vesicles. Fernández-Checa, JC; Kaplowitz, N; Ookhtens, M, 1993)	1.32
"Phenobarbital treatment enhanced glucuronidation of acetaminophen and structurally related compounds (i.e., p-nitrophenol) similarly in both phenotypes, but the treatment failed to induce morphine UDPGT in the obese Zucker rat."	( Effect of genetic obesity and phenobarbital treatment on the hepatic conjugation pathways. Blouin, RA; Chaudhary, IP; McNamara, PJ; Robertson, LW; Tuntaterdtum, S, 1993)	1.3
"Phenobarbital-treated (0.75 mM) hepatocytes from fa/fa Zucker rats showed approximately a three-fold lower induction response based on measurements of CYP2B1/2B2 (R-17 cDNA probe) and CYP2B1 (oligo probe) mRNAs."	( Cytochrome P450 2B enzyme (CYP2B) induction defect following phenobarbital treatment in the fa/fa Zucker rat: molecular characterization. Bandyopadhyay, AM; Blouin, RA; Chaudhary, I; Gemzik, B; Parkinson, A; Robertson, LW, 1993)	1.25
"Phenobarbital pretreatment, which induced hepatic but not pulmonary CMT metabolism, protected against CMT-depended pneumotoxicity suggesting escape of an active CMT metabolite from the liver is not responsible for the pneumotoxic response."	( Pulmonary activation and toxicity of cyclopentadienyl manganese tricarbonyl. Blanchard, KT; Clay, RJ; Morris, JB, 1996)	1.02
"Phenobarbital pretreatment potentiated halothane-induced lipid peroxidation with 9- and 20-fold increases in plasma and liver F(2)-isoprostanes, respectively."	( Demonstration of halothane-induced hepatic lipid peroxidation in rats by quantification of F2-isoprostanes. Awad, JA; Franks, JJ; Horn, JL; Roberts, LJ, 1996)	1.02
"Phenobarbital treatment of Gunn recipients of jejunal transplants from Wistar rats normalizes serum bilirubin levels."	( The use of jejunal transplants to treat a genetic enzyme deficiency. Burgos, AA; Jaffe, BM; Martinez-Noack, M, 1996)	1.74
"Phenobarbital treatment "normalized" serum bilirubin levels in recipients of orthotopic Wistar jejunal grafts (group 4)."	( The use of jejunal transplants to treat a genetic enzyme deficiency. Burgos, AA; Jaffe, BM; Martinez-Noack, M, 1996)	1.02
"Phenobarbital treatment had the greatest effect on alpha-methylene hydroxylation while beta-naphthoflavone had the greatest effect on methyl hydroxylation."	( Modulation of the mutagenicity and metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by phenolic compounds. Castonguay, A; Miller, C; Teel, RW, 1996)	1.02
"Phenobarbital treatment was shown to be associated with a twofold increase in DNase I sensitivity of the CYP2B1/2 gene in the liver."	( Changes in chromatin structure and nuclear matrix association of the rat cytochrome P450 2B1/2 (CYP2B1/2) gene following induction with phenobarbital. Dutmer, AA; Horbach, GJ; Stroop, CJ, 1996)	1.22
"In phenobarbital-treated mice, interferon beta reduced the induction of total cytochrome P-450 (22%), the activities of pentoxyresorufin O-dealkylase (38%), benzyloxyresorufin O-dealkylase (30%), erythromycin N-demethylase (30%), 7-ethoxycoumarin O-deethylase (16%) and cytochrome P-450 2B1 (33%) and 3A (45%) proteins."	( Modulation of constitutive and inducible hepatic cytochrome(s) P-450 by interferon beta in mice. Cantoni, L; Carelli, M; Porras, MC; Rizzardini, M, 1996)	0.81
"Phenobarbital (PB) treatment was only started at the second course and was continued for the following courses at a p.o."	( Phenobarbital administration does not affect high-dose ifosfamide pharmacokinetics in humans. Lokiec, F; Santoni, J; Tubiana-Hulin, M; Weill, S, 1996)	2.46
"With phenobarbital treatment the total focal volume was 20% of the liver volume three weeks after PH, whereas the corresponding value in the case of 3-methylcholanthrene was only 1%."	( Induced drug resistance inhibits selection of initiated cells and cancer development. Eriksson, LC; Rissler, P; Torndal, UB, 1997)	0.75
"Phenobarbital treatment of experimental animals induces cytochrome P450 enzymes, and thus acts as a growth stimulus to the liver with both hyperplasia and hypertrophy; cessation results in reversion of liver to normal size with apoptosis playing a role."	( Reversal of phenobarbital-induced hyperplasia and hypertrophy in the livers of lpr mice. Alison, MR; Edwards, RJ; Horgan, M; Sarraf, CE, 1997)	1.4
"Phenobarbital pretreatment of rats enhanced the in vitro conversion of 1,4-DCB and the amount of covalent binding."	( Species and strain differences in the hepatic cytochrome P450-mediated biotransformation of 1,4-dichlorobenzene. Hissink, AM; Oudshoorn, MJ; Van Bladeren, PJ; Van Ommen, B, 1997)	1.02
"In phenobarbital treated animals striatal injection of 1 microg of MPP+ did not produce any effect on dopaminergic parameters but injection of 2 microg of MPP+ caused losses of dopamine levels and dopamine transporter although smaller than in control rats."	( In vivo protection of striatal dopaminergic system against 1-methyl-4-phenylpyridinium neurotoxicity by phenobarbital. Cano, J; Machado, A; Merino, M; Vizuete, ML, 1997)	1.03
"Phenobarbital treatment increased the cytochrome P-450 amount and the p-nitrophenol (p-NPh) formation rate in hepatocytes from female and male rats to the same extent."	( Sex differences in biotransformation of the xenobiotic p-nitroanisole in isolated rat hepatocyte under the influence of phenobarbital. Mazur, SP, 1997)	1.23
"Phenobarbital pretreatment in vivo resulted in marked induction of such transport."	( High affinity uptake by isolated rat hepatocytes of a linear pseudo-hexapeptide, ditekiren. Kim, RB; Perry, PR; Wilkinson, GR, 1997)	1.02
"Phenobarbital treatment of flies leads to a rapid increase in the level of CYP6A2 mRNA and to an increased production of the CYP6A2 protein."	( The Drosophila cytochrome P450 gene Cyp6a2: structure, localization, heterologous expression, and induction by phenobarbital. Amichot, M; Brun, A; Dunkov, BC; Feyereisen, R; Ffrench-Constant, RH; Guzov, VM; Mocelin, G; Shotkoski, F, 1997)	1.23
"Phenobarbital pretreatment significantly decreased the AUC values for (R)-IF and (S)-IF, to 21 and 30% of the control values, respectively, and shortened plasma half-lives for both enantiomers [half-life for (R)-IF, 19.8 min; half-life for (S)-IF, 19.4 min]."	( Effects of phenobarbital on stereoselective metabolism of ifosfamide in rats. Chan, KK; Lu, H; Wang, JJ; Young, D, 1998)	1.41
"Phenobarbital (PB)-pretreatment of mice induced P450s 3A and 2B and markedly increased serum alanine aminotransferase (ALT) activity after cocaine or norcocaine administration."	( Effect of cytochrome P450 inducers on cocaine-mediated hepatotoxicity. Bornheim, LM, 1998)	1.02
"Phenobarbital-pretreatment increased the formation of M1-M3 in both rat strains (2-4 fold)."	( Genistein metabolism in liver microsomes of Wistar and mutant TR(-)-rats. Herzog, W; Jäger, W; Sartori, M; Thalhammer, T, 1998)	1.02
"Phenobarbital-treatment caused a significant induction of the activities of erythromycin N-demethylase and testosterone 6 beta-hydroxylase, but did not affect those of the other phase I enzymes and the other testosterone hydroxylases."	( Modulation of snake hepatic cytochrome P450 by 3-methylcholanthrene and phenobarbital. Bani, MH; Fukuhara, M; Kimura, M; Ushio, F, 1998)	1.25
"Phenobarbital treatment caused increases in liver:body weight ratios and histologic evidence of centrilobular hepatocellular hypertrophy."	( Phenobarbital does not promote hepatic tumorigenesis in a twenty-six-week bioassay in p53 heterozygous mice. Alden, CL; Bunch, RT; Curtiss, SW; Davila, JC; Morris, DL; Sagartz, JE, )	2.3
"Phenobarbital treatment increased the number of CYP2A5-positive centrilobular hepatocytes and the CYP2A5-positive areas were extended into the middle zone in all strains, but periportal hepatocytes remained negative."	( Expression of cytochrome P450 2A5 in preneoplastic and neoplastic mouse liver lesions. Bursch, W; Camus-Randon, AM; Grasl-Kraupp, B; Lang, MA; Rossmanith, W; Schulte-Hermann, R; Wastl, UM, 1998)	1.02
"Only phenobarbital-pretreatment produced increases in LDH leakage from cultures exposed to cocaine."	( Ethanol does not increase the hepatotoxicity of cocaine in primary rat hepatocyte culture. Abdel-Rahman, MS; Figliomeni, ML, 1998)	0.76
"Phenobarbital treatment induced ethylmorphine N-demethylation activity, but did not affect N-demethylation activity, towards chlorimipramine and chlorpromazine."	( N-Dealkylation of chlorimipramine and chlorpromazine by rat liver microsomal cytochrome P450 isoenzymes. De Matteis, F; Frosini, M; Palmi, M; Sgaragli, G; Valoti, M, 1998)	1.02
"Phenobarbital-treatment (20 mg kg-1 day-1 for 3 days; i.p.) significantly increased the plasma dimethadione (DMO)/TMO ratios at 0.08, 0.5, 1 and 2 h one's appropriate controls."	( Trimethadione metabolism and microsomal monooxygenases in untreated and phenobarbital-treated rhesus monkeys. Horie, T; Kitada, M; Ohmori, S; Sawa, Y; Tanaka, E; Taniguchi, T, 1998)	1.25
"Phenobarbital treatment has been observed to be negatively associated with bladder cancer risk in a few studies. "	( Barbiturates, smoking, and bladder cancer risk. Bull, SA; Friedman, GD; Habel, LA, 1998)	1.74
"Phenobarbital treatment increased hyper-sensitivity in liver in both regions."	( Tissue-specific chromatin structure of the phenobarbital-responsive unit and proximal promoter of CYP2B1/2 and modulation by phenobarbital. Kemper, B; Kim, J; Rivera-Rivera, I, 2000)	1.29
"Phenobarbital pretreatment potentiated thioacetamide necrogenicity, and this potentiation was parallel to the induction of the microsomal FAD monooxygenase system, both by phenobarbital and by thioacetamide itself."	( Potentiation of thioacetamide hepatotoxicity by phenobarbital pretreatment in rats. Inducibility of FAD monooxygenase system and age effect. Andrés, D; Cascales, M; Sarrión, D; Zaragoza, A, 2000)	1.28
"Phenobarbital treatment did not affect the control group."	( Cytochrome P450 activity and endothelial dysfunction in insulin resistance. Hoenig, M; Katakam, PV; Miller, AW; Ujhelyi, MR, )	0.85
"Phenobarbital pretreatment potentiates NDPS and N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS, a nephrotoxic metabolite of NDPS) nephrotoxicity in male rats."	( Gender differences in the potentiation of N-(3,5-dichlorophenyl)succinimide metabolite nephrotoxicity by phenobarbital. Anestis, DK; Ball, JG; Brown, PI; Hong, SK; Rankin, GO; Valentovic, MA, 2001)	1.25
"Phenobarbital (PB) treatment led to significant increases in all measured hepatic parameters and in total P450 of each investigated organ with the exception of ileum and caecum."	( Differential effects of phenobarbital on the constitutive and inducible expression of P450 2B and 3A subfamilies in sheep tissues. Alvinerie, M; Braun, JP; Dupuy, J; Galtier, P; Larrieu, G, 2001)	1.34
"Phenobarbital pretreatment enhanced this step and was not affected by gonadectomy."	( Metabolism of territrem a in liver microsomes from wistar rats: 2. Sex differences and regulation with gonadal hormones and phenobarbital. Lin, JL; Peng, FC; Wu, SW, 2001)	1.24
"Phenobarbital pretreated hepatocytes contained significantly higher total cytochrome P450 content than the control hepatocytes."	( Itraconazole- and fluconazole-induced toxicity in rat hepatocytes: a comparative in vitro study. Hassim, SM; Samsudin, SH; Somchit, N, 2002)	1.04
"Phenobarbital treatment enhanced production of fluroxene metabolites, including the highly toxic trifluoroethanol."	( Fluroxene toxicity induced by phenobarbital. Embro, WJ; Fiserova-Bergerova, V; Holaday, DA; Malagodi, MH; Munson, ES; Perry, JC; Shields, RP; Tham, MK, 1975)	1.26
"Phenobarbital treatment and metyrapone change the metabolic profile via induction and inhibition, respectively, and, thus, in the case of 1,4-benzodiazepines, the formation of metabolites with varying pharmacological activity."	( Effects of enzyme induction and inhibition on microsomal oxidation of 1,4-benzodiazepines. Beyer, KH; Hilderbrandt, AG; Sadée, W; Schwandt, HJ, 1976)	0.98
"Phenobarbital treatment also stimulated hydroxylations at C-23, C-24alpha, and C-26."	( Cholic acid biosynthesis: conversion of 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol into 5beta-cholestane-3alpha,7alpha, 12alpha,24beta,25-pentol by human and rat liver microsomes. Cheng, FW; Dayal, B; Mosbach, EH; Salen, G; Setoguchi, T; Shefer, S; Tint, GS, 1977)	0.98
"In phenobarbital-pretreated rats, there was an approximately 40% increase in the hepatic clearance due to a concomitant increase in the mean extraction ratio from 0.16 to 0.26."	( Disposition of carbamazepine and its 10,11-epoxide metabolite in the isolated perfused rat liver. Rane, A; Shand, DG; Wilkinson, GR, )	0.65
"Phenobarbital pretreatment significantly increased the biliary excretion following iopanoate administration but had no effect on that following iopanoate glucuronide."	( Biliary excretion of iopanoate glucuronide by the rat. Cooke, L; Cooke, WJ, )	0.85
"Phenobarbital pretreatment (75 mg/kg i.p."	( Hepatic microsomal induction and hepatic transport. Fischer, E; Gregus, Z; Varga, F, 1979)	0.98
"When phenobarbital pretreatment was omitted or when the substrate concentration was increased to 164 microM bilirubin, proportionally more BMG and less BDG were formed."	( Bilirubin diglucuronide synthesis by a UDP-glucuronic acid-dependent enzyme system in rat liver microsomes. Blanckaert, N; Gollan, J; Schmid, R, 1979)	0.71
"Phenobarbital treatment was also attended by a decrease in the intrahepatic content of [(3)H]vitamin D(3) (11.7+/-0.4 vs."	( Phenobarbital-induced alterations in the metabolism of [3H]vitamin D3 by the perfused rachitic rat liver in vitro. Avioli, LV; Baran, DT; Fausto, AC; Karl, I; Roberts, ML, 1979)	2.42
"Phenobarbital treatment increased the concentration of Ya and Yb in the liver, but had little effect on Yc."	( Ligandin heterogeneity : evidence that the two non-identical subunits are the monomers of two distinct proteins. Bass, NM; Kirsch, RE; Marks, I; Saunders, SJ; Tuff, SA, 1977)	0.98
"Phenobarbital pretreatment provided little or no protection."	( Iodipamide hepatotoxicity in the rat. Barnhart, JL; Burk, RF, 1979)	0.98
"Phenobarbital-pretreated rats anesthetized with halothane, 1 per cent, at FIO2 0.21 had only minor morphologic changes at 24 hours."	( An animal model of halothane hepatotoxicity: roles of enzyme induction and hypoxia. Brown, BR; McLain, GE; Sipes, IG, 1979)	0.98
"Phenobarbital treatment leads to a decrease of the total biliary excretion of metabolites to about 200 microgram/100 g bw/h, the metabolite pattern remaining unchanged."	( Alternative transport pathways of cholephilic 14C-hexobarbital metabolites in rats with experimental hepatitis and cholestasis. Buschmann, J; Joeres, R; Richter, E; Zilly, W, 1979)	0.98
"The phenobarbital-treated infants had a slower postnatal rise of indirect bilirubin than did nontreated controls."	( Indications for early exchange transfusion in patients with erythroblastosis fetalis. Depp, R; Heinrichs, WL; Wennberg, RP, 1978)	0.74
"Phenobarbital treatment (80 mg/kg x day) stimulates 5 alpha-reduction of cortisol per g of microsomes almost twofold."	( Effect of alcohol on microsomal cortisol 4en-5 alpha-reductase in the liver of rats fed on a standard or low protein diet. Bode, C; Bode, JC; Martini, GA, 1978)	0.98
"Phenobarbital pretreatment increased and CoCl2 pretreatment decreased trichloroethylene hepatotoxicity."	( Metabolic activation of trichloroethylene into a chemically reactive metabolite toxic to the liver. Allemand, H; Benhamou, JP; DeGott, C; Descatoire, V; Feldmann, G; Pessayre, D, 1978)	0.98
"Phenobarbital pretreatment increased 2-hexanol urinary excretion in both solvent treatment groups."	( Biotransformation of n-hexane and methyl n-butyl ketone in guinea pigs and mice. Abdel-Rahman, MS; Couri, D; Hetland, LB, 1978)	0.98
"In phenobarbital-treated rats, there was a significant plasma increase of the total concentration of free amino acids."	( Pattern and concentration of free amino acids in the plasma and liver tissue of phenobarbital-treated rats. Antoniello, S; Budillon, G; Cacciatore, L; Cerini, R; De Marco, F; De Ritis, F; Mazzacca, G, 1978)	1
"Phenobarbital pretreatment reduced CPA and phosphoramide mustard CXT (concentration x time) by 66+% and 27+%, respectively."	( Effect of phenobarbital on plasma levels of cyclophosphamide and its metabolites in the mouse. Alberts, DS; Chen, HS; Peng, YM; Struck, RF, 1978)	1.38
"Phenobarbital pretreatment had no significant effect on serum levels or the half-life of meperidine."	( The effect of phenobarbital on the metabolism of meperidine in normal volunteers. Schwartz, I; Stambaugh, JE; Wainer, IW, 1978)	1.34
"Phenobarbital treatment of animals can greatly modify the biotransformation and toxicity of styrene, phenobarbital inducible P-450 hemoprotein playing a predominant role in its metabolism."	( Interaction of styrene and acetone with drug biotransformation enzymes in rat liver. Vainio, H; Zitting, A, 1978)	0.98
"Phenobarbital pretreatment caused no significant change in the hepatic uptake of BSP or BSP-GSH."	( Hepatic transport of sulphobromphthalein and sulphobromphthalein-glutathione conjugate in control and phenobarbital-pretreated rats. Fischer, E; Gógl, A; Gregus, Z, 1978)	1.19
"Phenobarbital pretreatment eliminated the antitumor activity of BCNU and reduced the activity of PCNU and CCNU."	( The effect of phenobarbital pretreatment on the antitumor activity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl-1-nitrosourea (PCNU), and on the plasma p Byrd, A; Finn, A; Levin, VA; Stearns, J; Weinkam, RJ, 1979)	1.34
"Phenobarbital pretreatment of pregnant mice (ASH/TO strain) gave rise to approximately equal concentrations of phenobarbital in both maternal and fetal liver. "	( Delayed induction by phenobarbital of udp-glucuronyltransferase activity towards bilirubin in fetal liver. Burchell, B; Dutton, GJ, 1975)	2.02
"Phenobarbital treatment induced the activities of all drug enzymes and inhibited the lipid peroxidation in either sex during the period of thiamine deficiency."	( Hepatic drug metabolism and lipid peroxidation in thiamine deficient rats. Galdhar, NR; Pawar, SS, 1976)	0.98
"Phenobarbital treatment induced an increase in the cytochrome P-450 content that was different for the various subfractions."	( On the involvement of cytochrome P-450 in the binding of ribosomes to a subfraction of rat-liver rapidly sedimenting endoplasmic reticulum. Jergil, B; Ohlsson, R, 1977)	0.98
"Phenobarbital pretreatment potentiated the hepatic necrosis produced by both thioacetamide and thioacetamide sulfine."	( Thioacetamide-induced hepatic necrosis. I. Involvement of the mixed-function oxidase enzyme system. Holscher, MA; Hunter, AL; Neal, RA, 1977)	0.98
"Phenobarbital-treated RR rats maintained significantly lower blood acetaldehyde levels at 30, 90 and 150 minutes after ethanol injection compared to control RR animals."	( Role of liver cytosolic aldehyde dehydrogenase isozymes in control of blood acetaldehyde concentrations. Collins, AC; Deitrich, RA; Petersen, DR, 1977)	0.98
"Phenobarbital pretreatment yielded a 44 and 29% increase in BSP and DBSP Tm, respectively, whereas RB Tm remained unchanged."	( Biliary transport of cholephilic dyes: evidence for two different pathways. Berthelot, P; Dhumeaux, D; Duvaldestin, P; Mahu, JL, 1977)	0.98
"Phenobarbital treatment antagonized THC-induced reduction of fetal body weight, but did not reduce resorption rate."	( Alteration of delta 9-tetrahydrocannabinol-induced teratogenicity by stimulation and inhibition of its metabolism. Harbison, RD; Lubin, DJ; Mantilla-Plata, B, 1977)	0.98
"Phenobarbital pretreatment of the animals resulted ina significant increase in both the formation of TFAA and the cytochrome P-450 content of microsomes."	( The in vitro metabolism of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) by hepatic microsomal cytochrome P-450. Furukawa, T; Hirokata, Y; Karashima, D; Shigematsu, A, 1977)	0.98
"Phenobarbital treatment had no significant effect on the quantity of 34:2 but slightly increased that of 36:2 (significant at the 0.05 level)."	( Effects of ethionine and phenobarbital on the phosphatidylcholines of rat liver. Dyer, RA; Klopfenstein, WE, 1977)	1.28
"Phenobarbital pretreatment reduced injurious effect of furylfuramide on the liver with preservation of the centrolobular region."	( Furylfuramide-induced hepatic necrosis in mice and its modification by phenobarbital. Horiuchi, T; Ohtsubo, K; Saito, M, 1976)	1.21
"Phenobarbital-treated pups had higher opening pressures and fewer lamellar bodies than the control animals."	( The inhibition of pulmonary maturation in the fetal rabbit by maternal treatment with phenobarbital. Cashore, WJ; Douglas, W; Karotkin, EH; Kido, M; Oh, W; Redding, R; Stern, L, 1976)	1.2
"Phenobarbital-pretreated mice, inoculated i.p."	( Alterations in adriamycin efficacy by phenobarbital. Bachur, NR; Reich, SD, 1976)	1.25
"Phenobarbital pretreatment increased peroxidation due to exposure of the cells to CCl4 but not that associated with NADPH addition."	( Lipid peroxidation and alteration of membrane lipids in isolated hepatocytes exposed to carbon tetrachloride. Hornbrook, KR; McCay, PB; Weddle, CC, 1976)	0.98
"Phenobarbital pretreatment resulted in an enhancement in the total metabolism of AFB1 as well as in the formation of AFM1, AFQ1 and AFP1."	( Metabolism of aflatoxin B1 to aflatoxins Q1, M1 and P1 by mouse and rat. Dahms, R; Gurtoo, HL, 1976)	0.98
"Phenobarbital pretreatment of rats increased the biliary excretion of 14C after the administration of the 14C-labeled pyrrolidine and pyrroline metabolites, both of which undergo further metabolism."	( Role of metabolism in the biliary excretion of methadone metabolites. Hasegawa, AT; Roerig, DL; Wang, RI, 1976)	0.98
"Phenobarbital treatment does not alter the affinity of hexobarbital, but enhances the Ks value for aniline."	( The binding of hexobarbital and aniline to cytochrome P-450 of liver microsomes from control and phenobarbital-treated rats of different ages. Klinger, W; Müller, D, 1976)	1.19
"Phenobarbital pretreatment (50 mg/kg/day for 3 days orally) of male Wistar rats increased Vmax of benzene in vitro hepatic microsomal biotransformation about 6-fold without changing Km. "	( Effect of phenobarbital pretreatment on in vitro enzyme kinetics and in vivo biotransformation of benzene in the rat. Gut, I, 1976)	2.1
"The phenobarbital pretreatment led to a significant increase of the biliary transportmaximum and the biliary concentration of Ioglycamide."	( Improvement of biliary excretion of ioglycamide by pretreatment with phenobarbital. Klapdor, R, 1976)	0.97
"Phenobarbital treatment caused an increase of the enzyme activity, sulfobromophthalein and [3-H]glutathione, in the second protein fraction."	( Studies on the relationship of hepatic anion-binding proteins and sulfobromophthalein-glutathione conjugation in normal and phenobarbital-treated rats. Arimura, K; Hirayama, C; Ibayashi, H; Irisa, T; Kawasaki, H; Sakaguchi, S; Tominaga, K, 1975)	1.18
"Phenobarbital treatment also increases the enzyme in late foetal and adult mice, abolishing the sex difference."	( Induction of UDPglucose dehydrogenase during development, organ culture, and exposure to phenobarbital. Its relation to levels of UDPglucuronic acid and overall glucuronidation in chicken and mouse. Dutton, GJ; Fyffe, J, 1975)	1.2
"Phenobarbital pretreatment enhances the reduction rate in all age groups."	( The NADPH-dependent cytochrome P-450 reduction in liver microsomes of rats of different ages with and without phenobarbital pretreatment. Klinger, W; Lübbe, H; Müller, D, 1975)	1.19
"Phenobarbital treatment resulted in hyperplasia of the agranular endoplasmic reticulum in liver cells."	( [Morphological study of the hepatocyte in cirrhotic patients treated with phenobarbital]. Alcántara, G; Herrera, E; Jiménez Cardoso, JM; Martín, L; Wusterhaus, AH, )	1.08
"Phenobarbital treatment greatly enhanced bromobenzene-induced GGT and LDH release into the lavage fluid in a dose-dependent manner."	( Potentiation of bromobenzene-induced pneumotoxicity by phenobarbital as determined by bronchoalveolar lavage fluid analysis. Carlson, GP; Day, BJ; DeNicola, DB, 1992)	1.25
"2. Phenobarbital treatment increased the total amount of cytochrome P-450."	( Microsomal ethanol-oxidizing system in Euglena gracilis. Similarities between Euglena and mammalian cell systems. Briand, J; Julistiono, H, 1992)	0.8
"As phenobarbital treatment did not protect against neuronal damage in CA3 or other regions of the hippocampus, the circuitry of the dentate gyrus was implicated as a locus of cellular alterations that influenced the development of kindling."	( Alteration of long-lasting structural and functional effects of kainic acid in the hippocampus by brief treatment with phenobarbital. Cavazos, J; Golarai, G; Sutula, T, 1992)	1.01
"Phenobarbital pretreatment of the rats did not affect any of these kinetic parameters."	( Rat liver metabolism and toxicity of 2,2,2-trifluoroethanol. Dunbar, D; Fraser, JM; Kaminsky, LS; Seaman, M, 1992)	1
"In phenobarbital-pretreated rats, MMPS administration had little effect on any renal functional parameter measured or urological morphology."	( Role of para-hydroxylation in phensuximide-induced urotoxicity in the Fischer 344 rat. Anestis, DK; Beers, KW; Brown, PI; Hubbard, JL; Nicoll, DW; Rankin, GO; Shih, HC, 1992)	0.8
"Phenobarbital treatment promoted the urinary excretion of all of the metabolites of toluene, especially after exposure to high toluene concentration."	( Effects of ethanol and phenobarbital treatments on the pharmacokinetics of toluene in rats. Nakajima, T; Wang, RS, 1992)	1.32
"Phenobarbital treatment blocked the appearance of TGF-beta 1 and TGF-beta 2 immunoreactivities at 1600 h, Day 4; however, a rebound in immunoreactivities was observed with the onset of the surge after a 1-day delay."	( Cell-type-specific localization of transforming growth factor-beta 2 and transforming growth factor-beta 1 in the hamster ovary: differential regulation by follicle-stimulating hormone and luteinizing hormone. Lu, B; Ogren, C; Roy, C; Roy, SK, 1992)	1
"Phenobarbital pretreatment also caused a shift in the morphologic site of necrosis from midzonal to peripheral lobular (zone 1) regions."	( Cocaethylene hepatotoxicity in mice. Harbison, RD; James, RC; Roberts, SM; Roth, L, 1992)	1
"Phenobarbital pretreatment decreased the in vivo t0.5,max from 27.0 to 15.6 min, and increased the Kd,app from 0.78 to 1.30 ml/kg for carbon tetrachloride mediated cytochrome P-450 loss."	( Effect of phenobarbital treatment on carbon tetrachloride-mediated cytochrome P-450 loss and diene conjugate formation. Moody, DE, 1992)	1.41
"Phenobarbital pretreatment accelerated rates of production of all nicotine metabolites except nornicotine and nicotine-1'-N-oxide, whereas cimetidine retarded rates of production of five metabolites."	( Nicotine metabolism in stumptailed macaques, Macaca arctoides. Jeszenka, EV; Kyerematen, GA; Morgan, M; Seaton, M; Vesell, ES, )	0.85
"Phenobarbital treatment induced a decrease in cerebral arteriovenous difference of glucose at P14 and no change at P10 and P21."	( Influence of early chronic phenobarbital treatment on cerebral arteriovenous differences of glucose and ketone bodies in the developing rat. Bomont, L; Nehlig, A; Schroeder, H, 1991)	1.3
"Phenobarbital treatment (60 mg/kg b."	( The influence of the radiation syndrome on cytochrome P450-dependent monooxygenation in rat liver. Bleyer, H; Klinger, W; Müller, D; Wölfle, G, 1991)	1
"phenobarbital(PB) ip treatment caused an increase in P-450 content, cytochrome C reductase.aminopyrine N-demethylase(AMD) and glutathione S-transferase(GST) activities by 78, 66, 270 and 52%, respectively."	( [Studies on correlation between liver drug metabolizing enzyme activities and microsomal membrane fluidity in phenobarbital treated rats]. Fu, LS; Peng, RX, 1991)	1.21
"Phenobarbital treatment increased mRNA levels in both genders."	( Effect of the aging process on the gender and phenobarbital dependent expression of glutathione S-transferase subunits in brown Norway rat liver. Callaerts, A; Coecke, S; Guillouzo, A; Morel, F; Rogiers, V; Van Bezooijen, CF; Vandenberghe, Y; Vercruysse, A; Verleye, G, 1991)	1.26
"The phenobarbital-treatment resulted in 7.9-fold and 4.8-fold increases in 2-hydroxylation and N-oxidation of strychnine, respectively."	( Site-selective oxidation of strychnine by phenobarbital inducible cytochrome P-450. Kaneko, H; Oguri, K; Ohkuma, T; Tanimoto, Y; Yoshimura, H, 1991)	1.03
"In phenobarbital treated Octodon degus, testosterone metabolic pathways were decreased, not inducible or absent."	( Drug metabolism in Octodon degus: low inductive effect of phenobarbital. Del Villar, E; Gaule, C; Sanchez, E; Vega, P, 1990)	1.04
"Phenobarbital treatment, however, induced nicotine clearance in lung approximately 2-fold."	( Nicotine metabolism in isolated perfused lung and liver of phenobarbital- and benzoflavone-treated rats. Foth, H; Kahl, GF; Looschen, H; Neurath, H, 1991)	1.25
"Phenobarbital pretreatment enhanced the toxicity of both CCl4 and CHCl3, alone and in combination."	( A CCl4/CHCl3 interaction study in isolated hepatocytes: non-induced and phenobarbital-pretreated cells. Borzelleca, JF; Clarke, EC; Condie, LW; Gennings, C; O'Hara, TM; Sheppard, MA, 1991)	1.23
"As phenobarbital treatment in young rats enhanced the symptoms of nephrotoxicity and metyrapone treatment in adult rats decreased the symptoms of nephrotoxicity, age-dependent differences in chromate nephrotoxicity may be linked to an increase in the enzymatic reduction of Cr(VI) with age."	( Influence of metyrapone and phenobarbital on sodium dichromate nephrotoxicity in developing rats. Appenroth, D; Bräunlich, H; Friese, KH; Gambaryan, S, 1990)	1.09
"Phenobarbital treatment caused an increase in ovulation rate that was most pronounced in thin ewes and those on the low-protein diet."	( Effects of phenobarbital, dietary protein intake, and ewe liveweight on ovulation rate and concentrations of plasma FSH and hepatic microsomal enzymes. Cope, B; McGowan, LT; McLaughlin, R; Payne, E; Peterson, AJ; Smith, JF, 1990)	1.39
"Phenobarbital treatment of rat cultures increased the total amount of cytochrome P450, activities catalyzed by IIB1/2 (benzyloxy- and pentoxyresorufin O-dealkylases) and ALA-S activity, and ALA-S mRNA."	( Role of heme in phenobarbital induction of cytochromes P450 and 5-aminolevulinate synthase in cultured rat hepatocytes maintained on an extracellular matrix. Bement, WJ; Guzelian, PS; Haugen, SA; Li, D; May, BK; Schuetz, EG; Sinclair, JF; Sinclair, PR, 1990)	1.35
"Phenobarbital pretreatment produced 58% stimulation in overall metabolism, whereas 3-methylcholanthrene pretreatment had no effect relative to control rats (5.4 nmol/mg protein/min)."	( Biotransformation of lovastatin--III. Effect of cimetidine and famotidine on in vitro metabolism of lovastatin by rat and human liver microsomes. Kari, PH; Lu, AY; Vyas, KP; Wang, RW, 1990)	1
"Phenobarbital treatment induces an isozyme(s) of liver microsomal cytochrome P450 susceptible to CCl4 and enhances the latter's lethality. "	( Phenobarbital pretreatment alters the localization of CCl4-induced changes in rat liver microsomal fatty acids. James, JL; Moody, DE; Smuckler, EA, 1990)	3.16
"Phenobarbital treatment of rabbits increased in vitro transcription of RNA for both the P450IIC1/2 and P450IIC4 gene subgroups but only slightly and transiently for the constitutive P450IIC3 gene."	( Structure of 5' regions and expression of phenobarbital-inducible rabbit cytochrome P450IIC genes. Bell, P; Chan, G; Govind, S; Kemper, B; Zhao, J, )	1.12
"Phenobarbital-treated rats had greater initial aminopyrine rate constant of elimination, but we saw a similar fall in aminopyrine rate constant of elimination of about 40% within 1 wk of bile duct excision to a value still above baseline aminopyrine rate constant of elimination of untreated controls."	( Phenobarbital influences the development of sodium retention in liver disease induced by bile duct ligation in the rat. Branch, RA; Wensing, G, 1990)	2.44
"Phenobarbital pretreatment (15 mg/kg, iv, 96 h) significantly reduced the duration of anesthesia."	( Effects of chloramphenicol, cimetidine and phenobarbital on and tolerance to xylazine-ketamine anesthesia in dogs. Amouzadeh, HR; Nossaman, BC; Sangiah, S, 1990)	1.26
"Phenobarbital pretreatment did not markedly enhance the functional nephrotoxicity induced by DPMS (0.4 mmol), but tubular necrosis was greater than observed in non-phenobarbital-pretreated rats receiving DPMS (1.0 mmol kg-1)."	( Acute toxicity induced by 2-aryl-N-methylsuccinimides. Brown, PI; Nicoll, DW; Rankin, GO; Shih, HC; Teets, VJ, 1990)	1
"Phenobarbital pretreatment had only minor effects on ESX- or MSX-induced renal effects, with no significant morphological changes detected between treated and pair-fed control groups.(ABSTRACT TRUNCATED AT 250 WORDS)"	( Acute effects of the antiepileptic succinimides on the urinary tract and potentiation of phensuximide-induced urotoxicity by phenobarbital. Brown, PI; Nicoll, DW; Rankin, GO; Teets, VJ, 1990)	1.21
"In phenobarbital-treated rats, all analogues reduced the level of the P-450 chromophore, whereas only 4-hexyl-DDC and 4-isopropyl-DDC lowered 7-pentoxyresorufin O-dealkylase activity, a catalytic marker for P-450b."	( Effects of 4-alkyl analogues of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine on hepatic cytochrome P-450 heme, apoproteins, and catalytic activities following in vivo administration to rats. Gelboin, HV; Marks, GS; Park, SS; Riddick, DS, 1990)	0.79
"Phenobarbital pretreatment significantly increased the biliary excretion of both non-metabolizable organic anions (rose bengal, eosin and amaranth) and the metabolizable bromsulphthalein (BSP). "	( Substrate and phenobarbital induction of the biliary excretion of exogenous organic anions in rats. Fischer, E; Varga, F, 1985)	2.07
"Phenobarbital pretreatment did not alter the ICG elimination half lives in 10-, 20- and 110-day-old rats."	( Hepatic elimination kinetics of organic anions in rats: developmental aspects and influence of phenobarbital. Barth, A; Hoppe, H; Klinger, W, 1986)	1.21
"Phenobarbital pretreatment increased the steady-state extraction ratio of chlorpyrifos to 0.94, but did not lead to the presence of chlorpyrifos oxon in effluent perfusate."	( Factors affecting the hepatic biotransformation of the phosphorothioate pesticide chlorpyrifos. Sultatos, LG, 1988)	1
"Phenobarbital pretreatment did not result in any increase in NDMA metabolism whereas there was a very significant (6-fold) increase in NDEA metabolism."	( Metabolism of N-nitrosodimethyl- and N-nitrosodiethylamine by rat hepatocytes: effects of pretreatment with ethanol. Gorsky, LD; Hollenberg, PF, )	0.85
"Phenobarbital pretreatment did not substantially alter the time course of toxicity induced with 20 mg/l monocrotaline water."	( Dose-response relationship in intoxication by the pyrrolizidine alkaloid monocrotaline. Hubbard, AK; Huxtable, RJ; Shubat, PJ, 1989)	1
"Phenobarbital treatment did not affect the maximal binding capacity or the affinity of the central benzodiazepine receptors for [3H]flunitrazepam in the cerebral cortex, hippocampus and olfactory bulb."	( Chronic phenobarbital administration affects GABA and benzodiazepine receptors in the brain and periphery. Fares, F; Gavish, M; Pick, CG; Weizman, A; Yanai, J, 1989)	1.43
"Phenobarbital treatment produced an initial elevation in the level of GABA."	( The effects of two anticonvulsants on amino acid levels in the developing rat cerebellum. Hannah, RS; Roth, SH; Spira, AW, 1989)	1
"Phenobarbital treatment resulted in increase of delta-aminolevulinate synthetase (ALAS) activity and a decrease in heme oxygenase (HO) activity."	( Long-term effects of phenobarbital on rat liver microsomal drug-metabolizing enzymes and heme-metabolizing enzyme. Hashimoto, Y; Kurata, N; Kuroiwa, Y; Masuko, T; Yoshida, T, 1989)	1.32
"Phenobarbital treatment of the selenium-deficient rats resulted in an increase in the level of total cytochrome P-450 50% of that observed with control rats and in a 10-fold increase in microsomal heme oxygenase."	( Modulation of the induction of rat hepatic cytochromes P-450 by selenium deficiency. Elswick, B; Wrighton, SA, 1989)	1
"Phenobarbital treatment (80 mg/kg daily i.p."	( Characterization of 3-methylcholanthrene effects on the rat glucocorticoid receptor in vivo. Grieu, F; Guenat, C; Sunahara, GI, 1989)	1
"Phenobarbital treatment causes both the appearance of a new cytochrome P-450 isozyme with a molecular mass of 56 kDa and the increase in the content of three isozymes with molecular masses of 54, 52.5 and 50 kDa."	( [The effect of phenobarbital and amidopyrine on the rate of decomposition of isoforms of cytochrome P-450 in mouse liver microsomes]. Adrianov, NV; Dovgiĭ, AI; Khaĭlov, PM, 1989)	1.35
"In phenobarbital pretreated rats, endotoxin decreased enzyme activities less than in untreated animals."	( Effect of endotoxin to differentially affect cytochrome P-450 monooxygenase activities of untreated rats and animals induced with phenobarbital or 3-methylcholanthrene. Coto, JA; Williams, JF, 1989)	1
"3. Phenobarbital treatment increased the activities of three NADPH generating enzymes, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and malic enzyme, suggesting that MPA and PB differ in their effects on the liver NADPH-producing system."	( Medroxyprogesterone acetate (MPA) enhances liver NADPH-generating enzyme activities in normal rats. Saarni, HU; Sotaniemi, EA; Stengård, JH, 1988)	0.79
"Phenobarbital treatment induced an increase of total NADH cytochrome c reductase on mitochondrial fraction in hippocampus and hypothalamus, and a decrease of cytochrome oxidase activity on non-synaptic mitochondrial fraction in hypothalamus and medulla oblongata."	( Phenobarbital and 6-aminonicotinamide effect on cerebral enzymatic activities related to energy metabolism in different rat brain areas. Benzi, G; Curti, D; Dagani, F; Marzatico, F, 1987)	2.44
"Phenobarbital treatment caused 50% decrease in the rate of ethanol oxidation and NADPH oxidation per nmol of P-450."	( Hydroxyl-radical production and ethanol oxidation by liver microsomes isolated from ethanol-treated rats. Cronholm, T; Ekström, G; Ingelman-Sundberg, M, 1986)	0.99
"Phenobarbital pretreatment of the dams (previously shown to reduce VPA serum concentrations and induce the omega- and omega-1 oxidation pathways) reduced the embryotoxicity of VPA."	( Valproic acid teratogenicity in mice after various administration and phenobarbital-pretreatment regimens: the parent drug and not one of the metabolites assayed is implicated as teratogen. Nau, H, 1986)	1.23
"Phenobarbital treatment had no significant effect on the amount of AFB remaining in the liver after two hours, but decreased the amount of AFB covalently bound to hepatic DNA by 55%."	( Effects of phenobarbital on the biliary excretion of aflatoxin P1-glucuronide and aflatoxin B1-S-glutathione in the rat. Bellamy, GM; Eaton, DL; Holeski, CJ; Monroe, DH, 1987)	1.38
"Phenobarbital (PB) treatment of rats increased microsomal DMBA metabolism in all extrahepatic tissues examined."	( Expression and function of three cytochrome P-450 isozymes in rat extrahepatic tissues. Christou, M; Jefcoate, CR; Wilson, NM, 1987)	0.99
"Phenobarbital treated subjects had serum lipoprotein profile typical of low risk of ischemic heart disease."	( The effects of phenobarbital on serum high density lipoprotein subfractions and apolipoproteins. Luoma, PV; Marniemi, J; Sotaniemi, EA, 1988)	1.35
"Phenobarbital pretreatment of females of the four inbred strains resulted in enhancement of the hepatotoxic response to cocaine in the C3H, DBA, and Balb mice."	( Sex and strain differences in the hepatotoxic response to acute cocaine administration in the mouse. Boyer, CS; Petersen, DR; Ross, D, 1988)	1
"Phenobarbital treatment increased liver weight and mean hepatocyte volume by 39 and 26%, respectively, while total DNA content did not change, thus indicating that the hepatomegaly results principally from hypertrophy rather than hyperplasia."	( Bile acid secretion and pool size during phenobarbital induced hypercholeresis. Alpini, G; Berk, PD; Jones, MJ; Kiang, CL; Okuda, H; Sorrentino, D; Tavoloni, N, 1988)	1.26
"Phenobarbital treatment induced changes which favored 1-nitropyrene-3-ol formation, and Aroclor-1254 and ethanol-induced changes which favored 1-nitropyren-6-ol and 1-nitropyren-8-ol formation."	( Oxidative metabolism of 1-nitropyrene by rabbit liver microsomes and purified microsomal cytochrome P-450 isozymes. Howard, PC; Koop, DR; Reed, KA, 1988)	1
"Phenobarbital treatment slightly increased the Vmax to 0.51 for E(2)17G whereas the Vmax for E(2)3G was unchanged (0.90) compared to controls."	( Coregulation of C3-hydroxyl versus C17-hydroxyl glucuronidation of beta-estradiol in pregnancy and after treatment with phenobarbital or ethinyl-estradiol. Connors, S; Vore, M, 1988)	1.2
"Phenobarbital treatment also caused a 15% increase in the serum HDL-cholesterol although it did not have any significant effect on the total serum cholesterol."	( Inhibition of thromboxane A2 synthesis in rats treated with phenobarbital. Haghighi, AZ; Pynadath, TI, 1987)	1.24
"Phenobarbital pretreatment increased the urinary excretion of APAP-glucuronide."	( In vivo and in vitro hepatotoxicity and metabolism of acetaminophen in Syrian hamsters. Lupo, S; Mico, BA; Rush, GF; Yodis, LA, 1987)	0.99
"Phenobarbital pretreatment of mice induced hepatic cytochrome P-450 content, as well as microsomal activation of azinphos-methyl in vitro, yet antagonized the acute toxicity of this pesticide in vivo."	( Metabolic activation of the pesticide azinphos-methyl by perfused mouse livers. Minor, LD; Sultatos, LG, 1987)	0.99
"Phenobarbital pretreatment did not modify the rate of caffeine elimination or the extent of 6-amino-5-[N-methylformylamino]-1,3-dimethyluracil formation."	( Metabolism of caffeine to 6-amino-5-[N-methylformylamino]-1,3-dimethyluracil in the isolated, perfused liver from control or phenobarbital-, beta-naphthoflavone- and 3-methylcholanthrene-pretreated rats. Abbruzzi, R; Bastone, A; Bianchi, M; Bonati, M; Catalani, P; Guaitani, A; Latini, R; Pantarotto, C; Szczawinska, K, 1987)	1.2
"Phenobarbital pretreatment, as expected, increased the rate of aminopyrine oxidation of isolated hepatocytes."	( Interrelationship between aminopyrine oxidation and gluconeogenesis in hepatocytes prepared from fructose-pretreated mice. Antoni, F; Bánhegyi, G; Garzó, T; Mandl, J, 1987)	0.99
"The phenobarbital treatment was devoid of action on hepatic ADH and ALDH."	( Effect of centrally acting drugs on ethanol detoxification enzymes in distinct rat brain regions. Messiha, FS, )	0.61
"Phenobarbital treatment led to stimulation of 4-hydroxyvalproic acid [(omega-1)-oxidation], 5-hydroxyvalproic acid and n-propylglutaric acid (omega-oxidation) excretion."	( Oxidation and glucuronidation of valproic acid in male rats--influence of phenobarbital, 3-methylcholanthrene, beta-naphthoflavone and clofibrate. Heinemeyer, G; Hildebrandt, AG; Nau, H; Roots, I, 1985)	1.22
"Phenobarbital treatment led to a 3- to 4-fold increase in the formation rate of (-)-M3G and (+)-M6G whereas the glucuronidation of (+)-morphine at position 3 was increased only marginally."	( Natural (-)- and unnatural (+)-enantiomers of morphine: comparative metabolism and effect of morphine and phenobarbital treatment. Gawronska-Szklarz, B; Rane, A; Svensson, JO, 1985)	1.2
"Phenobarbital treatment resulted in a significant increase in the metabolism of mitomycin C in both intact and tumor tissues under anaerobic conditions."	( Effects of hypoxia and phenobarbital treatment on the metabolism of mitomycin C in experimental animals. Hatano, H; Iida, S; Koen, H; Nomura, F; Ohnishi, K; Okuda, K; Tanabe, Y, )	1.16
"Phenobarbital (PBT) pretreatment did not alter the renal P-450 level, but both PCB and PBT pretreatments antagonized VDC nephrotoxicity."	( Acute nephrotoxicity of 1,1-dichloroethylene in the rat after inhalation exposure. Conolly, RB; Jackson, NM, 1985)	0.99
"Phenobarbital pretreatment caused marked increases in hepatic mRNA for both P-450s as early as 22 days after conception."	( Regulation of cytochrome P-450b and P-450e mRNA expression in the developing rat. Hybridization to synthetic oligodeoxyribonucleotide probes. Giachelli, CM; Omiecinski, CJ, 1986)	0.99
"Phenobarbital treatment induced a distribution phase with transition from a 1-compartment to a 2-compartment extravascular model."	( Effects of phenobarbital treatment on 3-methylindole toxicosis in ponies. Thomas, DE; Turk, MA, 1986)	1.38
"In phenobarbital-treated rats, the major phenobarbital-induced form accounts for approximately 50% of the total in both organs."	( Cytochrome P450 of small intestinal epithelial cells. Immunochemical characterization of the increase in cytochrome P450 caused by phenobarbital. Bonkovsky, HL; Gasser, R; Hauri, HP; Marti, U; Meyer, UA, 1985)	0.99
"Phenobarbital pretreatment of the rats, which is known to enhance hepatic microsomal activation of CP, protected against CP-induced urinary bladder toxicity and the depression of hepatic MFO activities."	( Effects of the induction of hepatic microsomal metabolism on the toxicity of cyclophosphamide. Bansal, SK; Gurtoo, HL; Pavelic, Z; Struck, RF, 1985)	0.99
"Phenobarbital pretreatment depressed heart rate, blood pressure and postganglionic cardiac sympathetic neural discharge."	( Effect of phenobarbital pretreatment on cardiac neural discharge and pentylenetetrazol-induced epileptogenic activity in the cat. Carnel, SB; Lathers, CM; Schraeder, PL, 1985)	1.39
"Phenobarbital pretreatment prevented the convulsions and pulmonary damage produced by a 50 mg/kg i.p."	( The acute toxicity of cyclopentadienyl manganese tricarbonyl in the rat. Hanzlik, RP; Hogberg, K; Penney, DA; Traiger, GJ, 1985)	0.99
"Phenobarbital treatment resulted in no amplification or rearrangement of PB P-450 genes."	( Induction of cytochrome P-450 by phenobarbital is mediated at the level of transcription. Phillips, IR; Pike, SF; Rabin, BR; Shephard, EA, 1985)	1.27
"Phenobarbital treatment brought about SER proliferation in a part of liver cells, in each group."	( Inducibility of the hepatic microsomal monooxygenase system experimentally reduced to a minimum amount/activity. Effect of hypophysectomy, partial hepatectomy and phenobarbital/toluene treatment on the hepatic polysubstrate monooxygenase system in rats. Barcza, G; Marton, J; Szeberényi, S; Ungváry, G, 1985)	1.19
"Phenobarbital (PB) pretreatment caused induction of quinidine metabolism."	( Kinetics of microsomal metabolism of quinidine in rats. Mico, B; Rakhit, A, 1985)	0.99
"Phenobarbital pretreatment of male rats induced four microsomal cytochrome P-450 enzymes, at least one of which has previously not been reported. "	( Isolation and comparison of four cytochrome P-450 enzymes from phenobarbital-induced rat liver: three forms possessing identical NH2-terminal sequences. Backes, WL; Gibson, GG; Jansson, I; Mole, JE; Schenkman, JB, 1985)	1.95
"Phenobarbital treatment, in contrast to its effect on the ASGP-R level, did not change the cell surface binding of concanavalin A on rat hepatocytes."	( Modulation of asialoglycoprotein receptor levels in rat liver by phenobarbital treatment. Evarts, RP; Marsden, ER; Thorgeirsson, SS, 1985)	1.23
"In phenobarbital-treated rats, the isozymic composition of the hepatic cytosolic glutathione S-transferases was changed after giving hepatotoxic chemicals; glutathione S-transferases 2-2(AA), 3-3(A), 1-2(B), 3-4(C), and 4-4 + 5-5(D + E) were present in cytosol from control rats, but only glutathione S-transferases cochromatographing with transferases 4-4 + 5-5(D + E) were detected in rats given carbon tetrachloride or bromobenzene."	( Alteration of hepatic glutathione S-transferases and release into serum after treatment with bromobenzene, carbon tetrachloride, or N-nitrosodimethylamine. Anders, MW; Aniya, Y, 1985)	0.78
"Phenobarbital treatment induced more NADH- and NADPH-peroxidase activity than did 3-methylcholanthrene treatment."	( Methyl ethyl ketone peroxide damage to cytochrome P-450 peroxidase activities. Ando, M; Tappel, AL, 1985)	0.99
"Phenobarbital-treated infants were over eight times more likely to experience IVH than were untreated infants."	( Effect of phenobarbital on motor activity and intraventricular hemorrhage in preterm infants with respiratory disease weighing less than 1500 grams. Marshall, RE; Miller, RH; Moore, JA; Porter, FL, 1985)	1.39
"The phenobarbital pretreatment induced aniline and acetanilide hydroxylase activity even in riboflavin-deficient animals."	( Hepatic drug hydroxylation and lipid peroxidation in riboflavin-deficient rats. Galdhar, NR; Patel, JM; Pawar, SS, 1974)	0.73
"Phenobarbital treatment markedly increased the aminopyrine-induced reduction of cytochrome P-450, but ethanol did not cause any redox changes of this cytochrome."	( Mixed function oxidase and ethanol metabolism in perfused rat liver. Hassinen, IE; Ylikahri, RH, 1972)	0.97
"2. Phenobarbital pretreatment of rabbits did not stimulate any of the glucuronyltransferase activities measured in either rough- or smooth-surfaced microsomes."	( The submicrosomal distribution of hepatic uridine diphosphate glucuronyltransferases in the rabbit. Fouts, JR; Gram, TE; Hansen, AR, 1968)	0.76
"Treatment with phenobarbital, alone or in combination with benzodiazepines, was associated with significantly lower odds of a return ED visit within three days compared with benzodiazepines alone [AOR 0.45 (95% CI 0.23, 0.88) p = 0.02 and AOR 0.33 (95% CI 0.15, 0.74) p = 0.007]."	( Return Encounters in Emergency Department Patients Treated with Phenobarbital Versus Benzodiazepines for Alcohol Withdrawal. Lebin, JA; Mudan, A; Murphy, CE; Smollin, CG; Wang, RC, 2022)	1.3
"A treatment with phenobarbital was then begun and bilirubin level progressively decreased, with a complete and persistent normalization."	( Gilbert or Crigler-Najjar syndrome? Neonatal severe unconjugated hyperbilirubinemia with P364L UGT1A1 homozygosity. Civeriati, D; Cozzi, L; Degrassi, I; Nebbia, G; Nuti, F; Paolella, G, 2022)	1.05
"Treatment with phenobarbital was effective; 9 days after delivery the newborn was discharged without further treatment."	( [Neonatal abstinence syndrome after maternal use of tramadol]. de Wit, D; Koomen-Botman, I, 2013)	0.73
"Treatment with phenobarbital and potassium bromide completely terminated the seizures within 10days."	( Successful treatment of migrating partial seizures in Wolf-Hirschhorn syndrome with bromide. Itakura, A; Maegaki, Y; Nishimura, Y; Ohno, K; Okazaki, T; Saito, Y; Sejima, H; Yamamoto, T, 2016)	0.77
"Treatment with phenobarbital, a potent CYP inducer, increased the predominance of expression of these three mRNAs in WI rats (by 26-, 4-, and 2-fold, respectively) along with the predominance of increased microsomal total P450 contents and smooth-surface endoplasmic reticulum in the centrilobular hepatocytes."	( Strain differences in hepatic cytochrome P450 1A and 3A expression between Sprague-Dawley and Wistar rats. Hayashi, M; Kishida, T; Kuroda, J; Murakami, M; Muto, S; Tanaka, S; Tsutsui, M, 2008)	0.69
"Treatment with phenobarbital resulted in substantial improvement in the number of seizure episodes, however fine seizure-like movement continued in both of the hands, feet and in the tongue until the five-month follow-up."	( Prenatal diagnosis of fetal seizure: a case report. Huh, CY; Jung, E; Lee, BY, 2008)	0.69
"Treatment with phenobarbital resulted in a rapid and dramatic resolution of clinical signs."	( Phenobarbital-responsive sialadenosis associated with an esophageal foreign body in a dog. Gilor, C; Gilor, S; Graves, TK, )	1.91
"Pretreatment with phenobarbital (PB) or dexamethasone (DEX) resulted in a similar significant increase in TRA metabolic activity."	( Metabolism of territrem a in liver microsomes from male wistar rats: 3. Cytochrome p-450 isoforms catalyzing tra metabolism. Lin Wu, SW; Peng, FC, 2002)	0.64
"Pretreatment with phenobarbital i.p."	( Quinolinic acid promotes seizures and decreases glutamate uptake in young rats: reversal by orally administered guanosine. de Oliveira, DL; Frizzo, ME; Horn, JF; Moriguchi, E; Rodrigues, JM; Souza, DO; Wofchuk, S, 2004)	0.65
"Treatment by phenobarbital markedly reduced the rate of 25-hydroxylation by primary hepatocytes and suppressed the cellular CYP27A1 mRNA levels."	( Phenobarbital suppresses vitamin D3 25-hydroxylase expression: a potential new mechanism for drug-induced osteomalacia. Ellfolk, M; Hosseinpour, F; Norlin, M; Wikvall, K, 2007)	2.14
"Treatment with phenobarbital or phenytoin caused a reduction in seizure frequency, but did not improve EEG background or prevent death."	( The natural history and treatment of epilepsy in a murine model of tuberous sclerosis. Erbayat-Altay, E; Gutmann, DH; Wong, M; Xu, L; Zeng, LH, 2007)	0.68
"Pretreatment with phenobarbital and beta-naphthoflavone selectively altered the rate of formation of specific dihydrodiols by rat liver microsomes."	( Metabolism of 2-methylnaphthalene to isomeric dihydrodiols by hepatic microsomes of rat and rainbow trout. Breger, RK; Franklin, RB; Lech, JJ, )	0.45
"Pretreatment with phenobarbital significantly reduced the excretion of the (S) isomer in male and female mice and in male rats, and significantly reduced the excretion of the (R) enantiomer in male rats only."	( Disposition of (R,S)-tocainide. Some stereoselective aspects. French, TA; Gal, J; Haroldsen, PE; Zysset, T, )	0.45
"Pretreatment with phenobarbital reduced excretion of 3-methyl-s-triazolo[3,4-a]phthalazine."	( Studies on the in vivo metabolism of hydralazine in the rat. Streeter, AJ; Timbrell, JA, )	0.45
"Pretreatment with phenobarbital (PB), Aroclor 1254 (PCB) or beta-naphthoflavone (BNF) increased the cytochrome P-450 content and the various cytochrome P-450-mediated reactions up to 7-fold in larvae."	( Comparison of cytochrome P-450-dependent metabolism in different developmental stages of Drosophila melanogaster. Atuma, S; Blanck, A; Hällstöm, I, 1983)	0.59
"Treatment with phenobarbital causes an increased urinary excretion of tetrahydroxylated bile acids in patients suffering from intrahepatic cholestasis. "	( The isolation of tetrahydroxy bile acids as methyl esters from human urine and their characterization by 1H- and 13C-nuclear magnetic resonance spectroscopy. Back, P; Fritz, H; Populoh, C, 1984)	0.62
"Pretreatment with phenobarbital only prevents the propyphenazone-dependent GSH-depletion, but cobaltous chloride has no effect."	( [Effect of pyrazolone derivatives on the level of reduced glutathione in rat liver]. Bien, E, 1983)	0.59
"Pretreatment with phenobarbital enhanced the toxic response of renal cortical slices to CHCl3 in vitro as indicated by decreased p-aminohippurate and tetraethylammonium accumulation."	( Mechanism of chloroform nephrotoxicity. IV. Phenobarbital potentiation of in vitro chloroform metabolism and toxicity in rabbit kidneys. Bailie, MB; Hook, JB; Newton, JF; Smith, JH, 1984)	0.85
"Pretreatment with phenobarbital resulted in a significant reduction in the area under the plasma concentration vs."	( The effect of phenobarbital and SKF 525A on tocainide pharmacokinetics in the rat. Axelson, JE; Venkataramanan, R, 1980)	0.95
"Pretreatment with phenobarbital/nikethamide resulted in the highest enzyme activity, using wet weight as reference."	( Influence of drugs on the bilirubin UDP-glucuronyltransferase activity and the concentration of Y and Z acceptor proteins in rat liver. Gmyrek, D; Grimmer, I; Gross, J; Klinger, W; Moller, R, 1981)	0.59
"Pretreatment with phenobarbital resulted in a significant difference between treated and untreated difference between treated and untreated animals."	( Some effects of phenobarbital dosing of dairy cattle on aflatoxin M1 and fat in milk. Barnhart, HM; McGrew, PB; Mertens, DR; Wyatt, RD, 1982)	0.93
"Treatment with phenobarbital for 4 days also caused a significant increase of phosphatidylcholine and phosphatidylethanolamine content in plasma membranes."	( Phenobarbital induction of cytochrome P-450 and UDP-glucuronosyltransferase in rabbit liver plasma membranes. Antoine, B; Magdalou, J; Ratanasavanh, D; Siest, G, 1982)	2.05
"The treatment with phenobarbital constantly results in a decrease of the unsaturation index of fatty acids both in lecithins and cephalins."	( Liver microsome phospholipids and cytochrome P.450 concentration in phenobarbital treated rats fed on different diets. Bereksi-Reguig, K; Escousse, A; Goudonnet, H; Mounié, J; Truchot, R, 1983)	0.82
"Pretreatment with phenobarbital, piperonyl butoxide (2 h), SKF 525-A, or small multiple doses of OOS protected against the OOS-induced elevated level of bronchopulmonary lavage LDH, and the other signs of delayed toxicity including morphological alteration of Clara cells."	( Effect of drug metabolism inducer and inhibitor on O,O,S-trimethyl phosphorothioate-induced delayed toxicity in rats. Fukuto, TR; Gandy, J; Hasegawa, L; Imamura, T, 1983)	0.59
"Treatment with phenobarbital does not alter the apparent Km, but greatly increases the Vmax of both nuclear styrene monooxygenase and styrene epoxide hydrolase."	( Induction of nuclear styrene monooxygenase and epoxide hydrolase in rat liver. Garattini, E; Gazzotti, G; Salmona, M, 1981)	0.6
"Pretreatment with phenobarbital increased the rate of elimination and decreased the total anticoagulant effect per dose of both enantiomers."	( Effect of induction and inhibition of drug metabolism on pharmacokinetics and anticoagulant activity of the enantiomers of phenprocoumon in rats. Jähnchen, E; Schmidt, W; Trenk, D, 1980)	0.58
"Pre-treatment with phenobarbital modulated the metabolic disposition of BZ-3."	( Safety evaluation of benzophenone-3 after dermal administration in rats. Abdel-Rahman, MS; Barat, SA; Okereke, CS, 1995)	0.61
"Pretreatment with phenobarbital, under conditions in which liver CYP2B1 levels and liver microsomal thiotepa desulfuration to yield TEPA are both markedly increased, did not alter thiotepa's short-term (24-hr) cytotoxicity, as judged by a tumor excision assay, nor did it affect the extent of bone marrow toxicity associated with drug treatment."	( Modulation of thiotepa antitumor activity in vivo by alteration of liver cytochrome P450-catalyzed drug metabolism. Chang, TK; Chen, G; Waxman, DJ, 1995)	0.61
"Rats treated with phenobarbital alone did not develop tumors after 20 months."	( Tamoxifen induces short-term cumulative DNA damage and liver tumors in rats: promotion by phenobarbital. Carthew, P; De Matteis, F; Dorman, BM; Edwards, RE; Heydon, RT; Martin, EA; Smith, LL; White, IN, 1995)	0.84
"Treatment with phenobarbital (80 mg/kg body weight, 4 days), ethanol (0.9 gm/kg body weight, 4 days), or diethylmaleate (3.9 mmol/kg body weight) resulted in changes in biliary glutathione secretion of +114%, -56%, and -95%, respectively, and in hepatic glutathione content of -0%, +25%, and -86%, respectively, when compared with control values."	( The role of glutathione in bile secretion of endogenous trace elements in rats. Dijkstra, M; Havinga, R; Kuipers, F; Smit, EP; Vonk, RJ, 1993)	0.63
"Treatment with phenobarbital was effective in 5 of 7 dogs."	( Behavioral changes associated with suspected complex partial seizures in bull terriers. Dodman, NH; Keen, CL; Knowles, KE; Moon-Fanelli, AA; Shuster, L; Tidwell, AS, 1996)	0.63
"Pretreatment with phenobarbital (75 mg/kg, i.p."	( Effects of cytochrome P450 2E1 modulators on the pharmacokinetics of chlorzoxazone and 6-hydroxychlorzoxazone in rats. Chen, L; Yang, CS, 1996)	0.62
"Treatment with phenobarbital, which increased steady-state RcGshT mRNA by five- to sixfold, RcGshT polypeptide, and biliary GSH secretion by onefold in controls, had a smaller effect on steady-state RcGshT-mRNA level in EHBR (by 1.5-fold) and did not increase RcGshT polypeptide or biliary GSH secretion."	( Alterations in glutathione homeostasis in mutant Eisai hyperbilirubinemic rats. Cai, J; Horie, T; Kaplowitz, N; Kuhlenkamp, J; Lu, SC; Sun, WM; Takenaka, O; Takikawa, H; Yi, J, 1996)	0.63
"Pretreatment with phenobarbital resulted in a more rapid excretion for the high-dose level and an overall higher urinary excretion."	( Dose-dependent kinetics and metabolism of 1,2-dichlorobenzene in rat: effect of pretreatment with phenobarbital. Hissink, AM; Van Bladeren, PJ; Van Ommen, B, 1996)	0.83
"Treatment with phenobarbital or, especially, 3-methylcholanthrene rendered normal rat hepatocytes resistant to the mitoinhibitory effect of 2-AAF."	( Induced drug resistance inhibits selection of initiated cells and cancer development. Eriksson, LC; Rissler, P; Torndal, UB, 1997)	0.64
"Pretreatment with phenobarbital (PB; 80 mg/kg body wt, i.p."	( Evidence for O-dealkylation of 7-pentoxyresorufin by cytochrome P450 2B1/2B2 isoenzymes in brain. Dhawan, A; Parmar, D; Seth, PK, 1998)	0.62
"Pretreatment with phenobarbital (PB), 3-methylcholanthrene (3MC), and PB plus 3MC elicited significant induction of multiple CYP enzymes in alligator, as detected by antibodies to CYP1A, CYP2B, CYP2C, CYP2E, CYP2K, and CYP3A."	( Immunochemical analysis of liver microsomal cytochromes P450 of the American alligator, Alligator mississippiensis. Bandiera, SM; Buhler, DR; Ertl, RP; Stegeman, JJ; Winston, GW, 1999)	0.63
"Pretreatment with phenobarbital, which induces CYP enzymes that detoxify IQ, decreased adducts in maternal liver and possibly placenta, but not in fetal tissues."	( DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in fetal tissues of patas monkeys after transplacental exposure. Anderson, LM; Grady, JJ; Jones, AB; Josyula, S; Lu, LJ; Nerurkar, PV; Salazar, JJ; Snyderwine, EG, 2000)	0.63
"Pretreatment with phenobarbital can minimize the occurrence of intolerable adverse events associated with the introduction of primidone."	( The "forgotten" cross-tolerance between phenobarbital and primidone: it can prevent acute primidone-related toxicity. Frey, M; Kanner, AM; Parra, J, 2000)	0.91
"Treatment with phenobarbital or TAM+phenobarbital resulted in time-dependent increases in liver weight compared with the corresponding controls."	( Tamoxifen mutagenesis and carcinogenesis in livers of lambda/lacI transgenic rats: selective influence of phenobarbital promotion. Davies, R; Fenwick, S; Smith, LL; Styles, JA; Walker, J; White, IN, 2001)	0.86
"Treatment with phenobarbital attenuates the increases in MABP and AUVC but not the decreases in TcPO(2) after endotracheal suctioning."	( Effects of phenobarbital on cerebral blood flow velocity after endotracheal suctioning in premature neonates. Brann, BS; Brubakk, AM; Burgess, GH; Oh, W; Stonestreet, BS, 2001)	1.04
"Pretreatment with phenobarbital strongly protected the hepatocytes against the cypermethrin induced loss of cell viability percentage and increased enzyme leakage percentage."	( The role of enzyme induction and inhibition on cypermethrin hepatotoxicity. Abdel-Rahman, MS; El-Tawil, OS, 2001)	0.63
"Treatment with phenobarbital (30 mg/kg) for 2 weeks increased succinate dehydrogenase activity in peripheral blood lymphocytes of male rats. "	( Effects of phenobarbital on activity of mitochondrial enzymes in peripheral blood lymphocytes and oxidative phosphorylation in liver mitochondria. Burbenskaya, NM; Komissarova, IA; Nartsissov, YR, 2001)	1.05
"Pretreatment with phenobarbital produced a dose-dependent protective effect against seizures. "	( Synergistic protection of allopregnanolone and phenobarbital against maximal electroshock seizures in mice. Lu, YQ; Yu, R, 2001)	0.9
"Pretreatment with phenobarbital increased, while pretreatment with a small dose of carbon tetrachloride decreased, this toxicity."	( Biotransformation, sex hormones, and toxicity of two volatile anesthetics in mice. Cascorbi, HF; Gesinski, RM; Komar, MK, 1976)	0.58
"2. Treatment with phenobarbital decreased the antipyrine half-life from 65 to 30 min, but did not significantly change the urinary metabolite profile."	( Studies on the different metabolic pathways of antipyrine in rats: influence of phenobarbital and 3-methylcholanthrene treatment. Breimer, DD; Danhof, M; Krom, DP, 1979)	0.81
"The treatment with phenobarbital, diphenylhydantoin and carbamazepine for 7 days decreased the basal cAMP values in CSF and partly inhibited the rise after the convulsions."	( Effect of convulsions and anticonvulsive drugs on cerebrospinal fluid cyclic AMP in rabbits. Myllylä, VV, 1976)	0.57
"Treatment with phenobarbital (80 mg/kg, i.p., per day, 4 X) enhanced UDP glucuronosyl-transferase, but brought about different effects on the other enzymes."	( Modifications of drug metabolism by disulfiram and diethyldithiocarbamate. II. D-Glucuronic acid pathway. Lang, M; Marselos, M; Törrönen, R, 1976)	0.6
"Treatment with phenobarbital (10 mg/kg) or methaqualone (50 mg/kg) or lithium (4 meq/kg) prolonged the narcosis induced by ethanol (5 g/kg) by 45, 269 and 107% respectively."	( Toxic interactions of ethanol with other central depressants: antagonism by naloxone to narcosis and lethality. Ho, AK; Ho, CC, 1979)	0.6
"Pretreatment with phenobarbital (80 mg/kg i.p."	( [The influence of ethanol, dithiocarb, diethylmaleate and phenobarbital on the metabolic elimination of halothane in rats (author's transl)]. Biltz, H; Siegers, CP; Wächter, S, 1979)	0.83
"Pretreatment with phenobarbital enhanced digitoxin toxicity in guinea-pigs. "	( Effect of phenobarbital pretreatment on digitoxin toxicity and biotransformation in guinea-pigs. Carvalhas, ML; Figueira, MA, 1979)	1
"Pretreatment with phenobarbital increased the metabolism of pentachlorophenol to tetrachloro-p-hydroquinone both in vivo and in vitro."	( Metabolism of pentachlorophenol in vivo and in vitro. Ahlborg, UG; Larsson, K; Thunberg, T, 1978)	0.58
"Pretreatment with phenobarbital reduced the effect of MMS sixfold, which can be explained by a reduction of alkylation found in the bone marrow."	( Factors affecting the induction of micronuclei at low doses of X-rays, MMS and dimethylnitrosamine in mouse erythroblasts. Jenssen, D; Ramel, C, 1978)	0.58
"Pretreatment with phenobarbital induced lithocholate glucuronyltransferase activity to 150.5% of controls."	( Induction and activation of rat liver microsomal bile salt glucuronyltransferase. Czygan, P; Fröhling, W; Kommerell, B; Stiehl, A, 1976)	0.58
"Pretreatment with phenobarbital increased the initial rate of elimination of 14C from the blood and increased the amount of acetaminophen glucuronide excreted in the urine."	( Effect of subacute dosing and phenobarbital and 3-methylcholanthrene pretreatment on the metabolism of acetaminophen in rats. Beaubien, AR; Thomas, BH; Zeitz, W, 1977)	0.87
"Pretreatment with phenobarbital or 3-methylcholanthrene, two inducers of the drug metabolizing system, potentiated the toxic effects of tyrosine."	( Evidence for the possible formation of a toxic tyrosine metabolite by the liver microsomal drug metabolizing system. David, JC, 1976)	0.58
"Pretreatment with phenobarbital significantly increased the defluorinase activities of all three agents."	( Metabolism in vitro of enflurane, isoflurane, and methoxyflurane. Greenstein, LR; Hitt, BA; Mazze, RI, 1975)	0.58
"Pretreatment with phenobarbital accelerated the elimination of both substances."	( Metabolism, tissue distribution and covalent binding of tripelennamine and its N-nitroso derivative in the rat. Gillette, JR; Krishna, G; Rao, GS, 1975)	0.58
"Pretreatment with phenobarbital, pregnenolone-16 alpha-carbonitrile or acetone induced phenytoin metabolism non-stereoselectively."	( Two-dimensional high-performance liquid chromatographic method to assay p-hydroxyphenylphenylhydantoin enantiomers in biological fluids and stereoselectivity of enzyme induction in phenytoin metabolism. Hsieh, CY; Huang, JD, 1992)	0.61
"Pretreatment with phenobarbital, which promotes free radical production, did not influence induction of MT synthesis following an injection of menadione or CCl4."	( Induction of metallothionein synthesis by menadione or carbon tetrachloride is independent of free radical production. Min, KS; Onosaka, S; Tanaka, K; Terano, Y, 1992)	0.61
"Treatment with phenobarbital resulted in a 2.7-fold increase in the 15N2 produced from 15N-labelled N-nitrosobutyl(4-hydroxybutyl)amine by hepatic S9."	( In vitro metabolism of bladder carcinogenic nitrosamines by rat liver and urothelial cells. Airoldi, L; De Gregorio, G; Fanelli, R; Magagnotti, C; Moret, M, 1992)	0.62
"Pretreatment of phenobarbital (PB) had no remarkable effect on the dichromate-induced nephrotoxicity."	( Nephrotoxicity of sodium dichromate depending on the route of administration. Kim, E; Na, KJ, 1991)	0.62
"Pretreatment with phenobarbital (PB, 3 x 80 mg/kg i.p.) increased the incidence of necrosis to 70% and shifted this damage to the midzonal region."	( Shifting necrosis: butylated hydroxytoluene (BHT) and phenobarbital move cocaine-induced hepatic necrosis across the lobule. Charles, SJ; Connolly, AK; Powell, CJ, 1991)	0.85
"Treatment with phenobarbital (4 mg/kg/day, P."	( [Benign familial neonatal convulsion: clinical features of the propositus and comparison with the previously reported cases]. Ishikawa, Y; Kibayashi, M; Minami, R; Okabe, M; Tachi, N; Wakai, S, 1990)	0.62
"Pretreatment with phenobarbital slowed the time course of acetylcholinesterase and hepatic aliesterase inhibition following parathion exposure, suggesting the induction of a detoxication pathway(s) to a greater extent than the induction of activation."	( Time course of inhibition of acetylcholinesterase and aliesterases following parathion and paraoxon exposures in rats. Chambers, HW; Chambers, JE, 1990)	0.6
"Pretreatment with phenobarbital (PB) significantly increased (60-85%) the activity of ECOD in neuronal and glial cells, while a 140% increase was observed in neuronal AHH activity."	( Cytochrome P-450 dependent monooxygenases in neuronal and glial cells: inducibility and specificity. Das, M; Dhawan, A; Parmar, D; Seth, PK, 1990)	0.6
"Treatment with phenobarbital or 2-allyl-2-isopropylacetamide slightly induced 5-aminolevulinate synthase activity."	( Induction of cytochrome P-450 and 5-aminolevulinate synthase activities in cultured rat hepatocytes. Bement, WJ; Guzelian, PS; Haugen, SA; Sinclair, JF; Sinclair, PR, 1990)	0.62
"Treatment with phenobarbital resulted in enhancement of cytochrome P-450 that was visualized in hepatocytes in all regions of the lobule."	( Distribution and induction sites of phenobarbital- and 3-methylcholanthrene-inducible cytochromes P-450 in murine liver: immunohistochemical localization with monoclonal antibodies. Forkert, PG; Gelboin, HV; Mirehouse-Brown, P; Park, SS, 1988)	0.89
"Pretreatment with phenobarbital (40 mg/kg, ip, once daily for 4 days) did not affect the duration of anesthesia significantly."	( Effects of some hepatic microsomal enzyme inducers and inhibitors on xylazine-ketamine anesthesia. Amouzadeh, HR; Qualls, CW; Sangiah, S, 1989)	0.6
"In untreated and phenobarbital-treated hepatocytes, 20% of protein kinase C activity was isolated with a membranous fraction, while 75% of the activity was membrane associated in TPA-treated hepatocytes."	( Independent mechanisms for tumor promoters phenobarbital and 12-O-tetradecanoylphorbol-13-acetate in reduction of epidermal growth factor binding by rat hepatocytes. Gibbs, TA; Jirtle, RL; Meyer, SA, 1989)	0.87
"Pretreatment with phenobarbital and 3-methylcholanthrene did not inhibit BSP-mediated increase of ODC and SAMDC."	( Induction of ornithine decarboxylase and S-adenosylmethionine decarboxylase by sulfobromophthalein in rats. Kuroiwa, Y; Numazawa, S; Oguro, T; Yoshida, T, 1989)	0.6
"Pretreatment with phenobarbital reduced, whereas previous application of tri-O-cresyl phosphate (TOCP) enhanced, effectiveness of soman administered i.p."	( Phrenic nerve-diaphragm preparation in situ for studying the detoxification of soman in the rat liver. Bosković, B; Cetković, S, 1988)	0.6
"Pretreatment with phenobarbital prevented seizure activity."	( 5-(2-Cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB): correlation of hypnotic and convulsant properties with alterations of synaptosomal 45Ca2+ influx. Chandler, LJ; Gonzales, R; Leslie, SW, 1986)	0.59
"Treatment with phenobarbital or primidone seemed not to affect CSF GABA levels."	( Low levels of gamma-aminobutyric acid in cerebrospinal fluid of dogs with epilepsy. Löscher, W; Schwartz-Porsche, D, 1986)	0.61
"The treatment with phenobarbital or PCB increased the activities of testosterone 16 alpha-hydroxylase, benzo(a)pyrene hydroxylase and aminopyrine N-demethylase more markedly in female rats than in male rats."	( Effects of phenobarbital, 3-methylcholanthrene and polychlorinated biphenyls on sex-specific forms of cytochrome P-450 in liver microsomes of rats. Kamataki, T; Kato, R; Maeda, K; Shimada, M, 1986)	0.98
"Treatment with phenobarbital (PB) and clofibrate (CF) does not modify DAO activity, while that with Aroclor 1254 (PCB) and beta-naphtoflavone (BNF) significantly decreases it."	( Induction and quail liver diamine oxidase (histaminase). Part II: Different responses to the inducers. Buffoni, F; Cintelli, A; Ignesti, G; Perretti, M, 1988)	0.61
"Rats treated with phenobarbital, which increases hepatic cytochrome P-450 content, or isoniazid, which does not increase hepatic cytochrome P-450 content, both metabolized more CCl4 than control rats as indicated by exhalation of greater quantities of CCl4 metabolites and by an increase in CCl4 toxicity."	( Inhibition of CCl4 metabolism by oxygen varies between isoenzymes of cytochrome P-450. Burk, RF; Hill, KE; Lane, JM, 1988)	0.6
"Treatment with phenobarbital showed no effect on any of the parameters investigated in either species."	( Species characteristics of the hepatic xenobiotic and steroid biotransformation systems of two teleost fish, Atlantic cod (Gadus morhua) and rainbow trout (Salmo gairdneri). Andersson, T; Förlin, L; Goksøyr, A; Hansson, T; Klungsøyr, J; Zhang, Y, 1987)	0.61
"Pretreatment with phenobarbital and Aroclor, inducers of hepatic P-450, on the other hand, had no effect on salicylate-induced nephrotoxicity nor on the covalent binding of [14C]salicylate equivalents to renal mitochondria."	( The effect of mixed function oxidase induction and inhibition on salicylate-induced nephrotoxicity in male rats. Kocsis, JJ; Kyle, ME, 1986)	0.59
"Pretreatment with phenobarbital shortened the stereotypy evoked by methamphetamine."	( Studies on the mechanism of interaction between methamphetamine and quinine in rats. Chiang, HJ; Kuroiwa, Y; Suzuki, T; Yanaura, S; Yoshida, T, 1986)	0.59
"Pretreatment with phenobarbital (PB) increased the renal toxicity of MeCCNU."	( In vivo studies on the relationship between hepatic metabolism and the renal toxicity of 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea (MeCCNU). Boyd, MR; Kramer, RA; McMenamin, MG, 1986)	0.59
"Pretreatment with phenobarbital increased not only the Vmax, but also the Km, for this binding."	( Metabolic activation of the tricyclic antidepressant amineptine--I. Cytochrome P-450-mediated in vitro covalent binding. Amouyal, G; Descatoire, V; Geneve, J; Larrey, D; Letteron, P; Pessayre, D; Tinel, M, 1987)	0.6
"Pretreatment with phenobarbital resulted in the precocious onset of PB-B in fetal and neonatal rat liver accompanied by an increase in classically associated monooxygenase activities."	( Cytochrome P-450 isoenzyme content and monooxygenase activities in rat liver: effect of ontogenesis and pretreatment by phenobarbital and 3-methylcholanthrene. Beaune, P; Celier, C; Cresteil, T; Guengerich, FP; Leroux, JP, 1986)	0.8
"Treatment with phenobarbital did not prevent pathologic changes in the hippocampus, dentate gyrus, and pyriform or prepyriform cortex."	( Does phenobarbital protect against trimethyltin-induced neuropathology of limbic structures? Chang, L; Woolley, D; Zimmer, L, 1985)	1.12
"Pretreatment with phenobarbital (0.1% solution for 7 days instead of drinking water) significantly decreased the amount of total AA recovered in bile, to 12.8% mainly as a consequence of reduced glucuronide excretion (3.5%), whereas the GSH-conjugate was augmented to 6.3%."	( Effects of phenobarbital, phorone and carbon tetrachloride pretreatment on the biliary excretion of acetaminophen in rats. Loeser, W; Siegers, CP, 1985)	0.98
"Pretreatment with phenobarbital markedly increased oxidative DES metabolism by renal microsomes from female rat but not from male rat."	( In vitro metabolism of diethylstilbestrol by hepatic, renal and uterine microsomes of rats and hamsters. Effects of different inducers. Haaf, H; Metzler, M, 1985)	0.59
"Pretreatment with phenobarbital led to a marked increase in binding of DES to kidney microsomes but not to liver microsomes from female hamsters and male and female rats."	( Covalent binding of diethylstilbestrol to microsomal protein in vitro correlates with the organotropism of its carcinogenicity. Haaf, H; Metzler, M, 1985)	0.59
"Pretreatment with phenobarbital (PB), dichlorodiphenyltrichloroethane (DDT), 3-methylcholanthrene (3-MC), beta-naphthoflavone (beta-NF) or Aroclor 1254 (ARO) produced a variable degree of inhibition of DMNd and had no significant effects on the response to DMN in the in vivo/in vitro HPC/DR assay."	( Effects of pretreatment with pyrazole and inducers of mixed function oxidases on DNA repair elicited by dimethylnitrosamine in rat hepatocytes in vivo and in vitro. Dietz, D; Kornbrust, D, 1985)	0.59
"Treatment with phenobarbital, but not ethanol, increased the amount of liver acetaldehyde dehydrogenase activity."	( Induction of liver acetaldehyde dehydrogenase: possible role in ethanol tolerance after exposure tobarbiturates. Cohen, G; Redmond, G, 1971)	0.59
"Treatment with phenobarbital resulted in only a slight increase in enzyme activity."	( Benzypyrene hydroxylase activity in isolated parenchymal and nonparenchymal cells of rat liver. Bresnick, E; Cantrell, E, 1972)	0.59

Toxicity

Phenobarbital (PB) enhanced the toxic response of renal cortical slices to CHCl3 in vitro as indicated by decreased p-aminohippurate and tetraethylammonium accumulation. Realisation of toxic effects of acrylamide may involve a decrease of the carbohydrate energy metabolism. In the intact organism these processes precede the induction of the phenobarbitals-dependent cytochrome P450.

Excerpt	Reference	Relevance
" Phenobarbital treatment enhanced production of fluroxene metabolites, including the highly toxic trifluoroethanol."	( Fluroxene toxicity induced by phenobarbital. Embro, WJ; Fiserova-Bergerova, V; Holaday, DA; Malagodi, MH; Munson, ES; Perry, JC; Shields, RP; Tham, MK, 1975)	1.45
" 3,4,3',4'-Tetrachlorobiphenyl was also toxic at a dose of 50 mg/kg, in keeping with its weak MC-type-inducing ability."	( Possible correlation between induction modes of hepatic enzymes by PCBs and their toxicity in rats. Miki, M; Ozawa, N; Yoshihara, S; Yoshimura, H, 1979)	0.26
" A connection is suggested between the first-pass metabolism in male rats and the hepatotoxicity, which is possibly mediated through a metabolite or intermediate formed in toxic amount during the first passage of the liver."	( Hepatotoxicity of citalopram in rats and first-pass metabolism. Fredricson Overø, K; Svendsen, O, 1978)	0.26
" Toxic effects of procaine were, therefore, concluded to be due to the accumulation of the drug in the brain."	( Effect of pretreatment with tricresylphosphates and phenobarbital on the metabolism and toxicity of procaine in rats. Moroi, K; Satoh, T, 1977)	0.51
" In both male and female animals the LD50 was reduced by one half as compared to control animals."	( Effect of phenobarbital pretreatment on digitoxin toxicity and biotransformation in guinea-pigs. Carvalhas, ML; Figueira, MA, 1979)	0.66
" The quail treated with a toxic dose of CAT had an increased level of thiobarbituric acid (TBA) reacting products in the liver, with a concomitant decrease in GSH content."	( Effects of 2-chloro-4-acetotoluidine (CAT) toxicity on biochemical and morphological alterations in quail. Barger, AE; Bickford, AA; Giri, SN, )	0.13
" It was found that high concentrations of beta-cyclodextrin were toxic to the animals in the single exchange technique employed."	( beta-Cyclodextrin as an aid to peritoneal dialysis. Renal toxicity of beta-cyclodextrin in the rat. Field, FP; Hansen, DA; Mufson, RA; Perrin, JH; Torosian, G, 1978)	0.26
" It is concluded that the toxic effects of barbiturates are partially due to the inhibition of mitochondrial respiration at the level of NADH-dehydrogenase."	( [Possible biochemical mechanism of the toxic effects of barbiturates]. Cheistiakov, VV; Ratnikova, LA, 1978)	0.26
"The effect of SKF-525A and phenobarbital on the LD50 values of vinblastine and vincristine suggests that the toxicity of these agents in mice does not arise from a toxic metabolite."	( Phenobarbital and SKF-525A on vinblastine and vincristine toxicity in mice. Fitzgerald, TJ, 1976)	2
" The enzymes involved in the toxic metabolic pathway have been investigated in this study."	( Rat liver metabolism and toxicity of 2,2,2-trifluoroethanol. Dunbar, D; Fraser, JM; Kaminsky, LS; Seaman, M, 1992)	0.28
" Oligomycin-sensitive Mg2(+)-ATPase was decreased significantly only starting at 6 hr (21%) after CCl4 administration, indicating that depletion of ATP at early time points was most likely due to rapid utilization consequent to toxic events."	( Altered hepatic energy status in chlordecone (Kepone)-potentiated CCl4 hepatotoxicity. Kodavanti, PR; Kodavanti, UP; Mehendale, HM, 1990)	0.28
" CD, known to potentiate hepatotoxic and lethal effects of halomethanes in rats, failed to potentiate the toxic effects of any of these three halomethanes in gerbils."	( Hepatotoxicity and lethality of halomethanes in Mongolian gerbils pretreated with chlordecone, phenobarbital or mirex. Cai, Z; Mehendale, HM, 1991)	0.5
" Prevalence of adverse effects was 12% and 4% in these two groups, respectively."	( [Evaluation of the prevalence of side effects of phenobarbital in patients in the Champagne-Ardenne region]. Delasnerie-Lauprêtre, N; Turpin, JC, 1991)	0.54
" Precocene II was significantly more toxic to hepatocytes cultured from PB-treated, compared with untreated, gerbils."	( Maintenance of monooxygenase activities and detection of cytochrome P-450-mediated cytotoxicity in Mongolian gerbil hepatocyte cultures. Fentem, JH; Fry, JR; Hammond, AH, 1991)	0.28
" Toxic blooms of this cyanobacteria have been reported throughout the temperate world."	( Evaluation of potential chemoprotectants against microcystin-LR hepatotoxicity in mice. Eldeen, ZM; Hermansky, SJ; Mereish, KA; Roche, VF; Stohs, SJ, 1991)	0.28
" Although the exact sequence of its hepatotoxic factors is unproven, it seems likely that lipid peroxidation through the dysfunction of antioxidant defence factors and a toxic metabolite contribute to the formation of this liver injury."	( Hepatotoxicity of diethyldithiocarbamate in rats. Hobara, T; Ishiyama, H; Kanbe, T; Ogino, K; Shimomura, Y, 1990)	0.28
" A rapid increase in the serum sodium concentration by 3 to 5 mmol/L with the use of hypertonic saline is safe and efficacious in managing acute symptomatic hyponatremia."	( Management of hyponatremic seizures in children with hypertonic saline: a safe and effective strategy. Fleischmann, L; Hackbarth, R; Meert, K; Sarnaik, AP, 1991)	0.28
" Oral administration of phenobarbital enhanced the toxic effect of RM on (b), (d) and (e) and did not modify the toxic effect of RM on (a), (c) and (f)."	( Glucosinolates toxicity in growing rats: interactions with the hepatic detoxification system. Nugon-Baudon, L; Rabot, S; Raibaud, P; Szylit, O, 1990)	0.59
" In retrograde perfusion under low oxygen supply with Ca2+, CCl4 produced essentially the same toxic manifestations as those observed in the anterograde perfusion."	( Effects of oxygen deficiency and calcium omission on carbon tetrachloride hepatotoxicity in isolated perfused livers from phenobarbital-pretreated rats. Masuda, Y; Nakamura, Y, 1990)	0.49
"1% seizure control rate), with adverse effects of sedation and intellectual depression."	( Plasma level distribution, effect and toxicity of antiepileptic drugs among Ethiopian epileptics. Abebe, Y; Bekele, G; T'Haimanot, R, 1990)	0.28
" Other features of this adverse drug reaction were unremitting fever, leukocytosis with eosinophilia and atypical lymphocytosis, and proteinuria."	( Phenobarbital hepatotoxicity in an 8-month-old infant. Goldbach, M; Phillips, MJ; Roberts, EA; Spielberg, SP, 1990)	1.72
"The oral LD50 of Crotalaria assamica, which contains mainly monocrotaline, was found to be 154 mg/kg in mice."	( A comparative study on the hepatic toxicity and metabolism of Crotalaria assamica and Eupatorium species. Chan, MY; Ogle, CW; Zhao, XL, 1989)	0.28
"7 mM TCA or TCL was not toxic compared with the same dose of TCE."	( Toxicity and metabolism of trichloroethylene in rat hepatocytes. Abdel-Rahman, MS; Farghali, H; Kadry, AM, 1989)	0.28
"The aim of the present study was to compare the reliability of LD50 determination using the traditional Litchfield and Wilcoxon method with that obtained by four alternative tests requiring smaller numbers of animals, for the purpose of classifying chemicals according to their acute toxicity."	( Comparison of five methods for the determination of lethal dose in acute toxicity studies. Carvalho, RR; Cunha, FQ; Fingola, FF; Freitas, JC; Menezes, MA; Paumgartten, FJ; Presgrave, OA, 1989)	0.28
" Pretreatment with PB and MC increased and TOCP decreased, whereas MeI as well as CoCl2 did not alter the LD50 value of soman in rats."	( Role of carboxylesterase in protection against soman toxicity. Purshottam, T; Srivastava, R, 1989)	0.28
"Mouse livers perfused in situ with the pesticide methyl parathion (O,O-dimethyl O-P-nitrophenyl phosphorothioate) resulted in the appearance of the toxic metabolite, methyl paraoxon (O,O-dimethyl-O-P-nitrophenyl phosphate), in the effluent perfusate."	( The role of the liver in mediating the acute toxicity of the pesticide methyl parathion in the mouse. Sultatos, LG, )	0.13
"trans-4-Acetylaminostilbene (trans-AAS) is acutely toxic to rats."	( Modulation of trans-4-acetylaminostilbene metabolism in the rat by methylcholanthrene and phenobarbital and its relevance for acute toxicity. Neumann, HG; Pfeifer, A, )	0.35
"The role of S-oxidation in the toxic bioactivation of alpha-naphthylisothiocyanate (ANIT) was investigated."	( Effect of inhibitors of alpha-naphthylisothiocyanate-induced hepatotoxicity on the in vitro metabolism of alpha-naphthylisothiocyanate. Hanzlik, RP; Traiger, GJ; Vyas, KP, 1985)	0.27
" It was concluded that, at the dose ranges studied, pretreatment with PB or PCB did not significantly alter the toxic effects produced by TCB."	( Effect of phenobarbital and polychlorinated biphenyls on the toxicity and disposition of 1,2,4,5-tetrachlorobenzene in the rat. Chu, I; Valli, VE; Villeneuve, DC; Yagminas, A, 1986)	0.67
" It is well established that the pneumotoxicity of MCT depends on its hepatic bioactivation to monocrotaline pyrrole (MCTP) and perhaps other toxic metabolites."	( Effect of a mixed function oxidase inducer and inhibitor on monocrotaline pyrrole pneumotoxicity. Bruner, LH; Carpenter, LJ; Hamlow, P; Roth, RA, 1986)	0.27
" We have hypothesized these lesions to be related to the adverse hepatic actions of MCT and other PAs."	( Modulation of monocrotaline-induced hepatic genotoxicity in rats. Petry, TW; Sipes, IG, 1987)	0.27
" Most of the adverse effects of this dose of phenobarbitone in the gerbil can thus be seen to be associated either with reproductive impairment or with exposure during sensitive periods of early development."	( Phenobarbitone: adverse effects on reproductive performance and offspring development in the Mongolian gerbil, (Meriones unguiculatus). Chapman, JB; Cutler, MG, 1988)	0.27
"2 and 3 times the LD50 value in rats."	( Pharmacokinetics and toxicity of mitomycin C in rodents, given alone, in combination, or after induction of microsomal drug metabolism. Kanyár, B; Kerpel-Fronius, S; Lelieveld, P; Pinedo, HM; Stuurman, M; Verwey, J, 1988)	0.27
" Indeed, although some form of side effect occurred in 50% of patients, treatment had to be changed in only 18% and the drug had to be stopped in only 7%."	( Clinical side effects of phenobarbital, primidone, phenytoin, carbamazepine, and valproate during monotherapy in children. Armijo, JA; Arteaga, R; Herranz, JL, )	0.43
" In contrast, only DEHP and BBS induced toxic renal lesions."	( The chronic hepatic or renal toxicity of di(2-ethylhexyl) phthalate, acetaminophen, sodium barbital, and phenobarbital in male B6C3F1 mice: autoradiographic, immunohistochemical, and biochemical evidence for levels of DNA synthesis not associated with car Anderson, LM; Diwan, BA; Hagiwara, A; Lindsey, K; Ward, JM, 1988)	0.49
" However, carbamazepine consistently produced fewer adverse effects on tests of attention/concentration and motor performance than did the other three antiepileptic drugs."	( Results of a nationwide Veterans Administration Cooperative Study comparing the efficacy and toxicity of carbamazepine, phenobarbital, phenytoin, and primidone. Collins, JF; Craft, B; Cramer, JA; Mattson, RH; Novelly, RA; Smith, DB, 1987)	0.48
" A toxic effect of isoflurane was not observed under identical experimental conditions."	( Comparative toxicity of halothane, isoflurane, hypoxia, and phenobarbital induction in monolayer cultures of rat hepatocytes. Costa, AK; Heffel, DF; Schieble, TM; Trudell, JR, 1988)	0.52
"Administration of phenobarbital, benzonal and benzobamil in a dose of 1/20 of LD50 to rats was shown to be followed by phase changes in the system of microsomal oxidation of the liver--activation in the first days after administration with the subsequent (in 1-3 months) decrease of the activity."	( [Effect of anticonvulsant agents, inducers of microsomal oxidation, on the B-link of immunity and on the natural cytotoxicity of lymphoid organ cells in rats]. Cherevko, NA; Galenko, OA; Novozheeva, TP; Potapova, GV; Saratikov, AS, )	0.47
" It was concluded that a metabolite(s) contributes to or is responsible for acute NDPS-induced nephrotoxicity and that at least 1 toxic metabolite might be of extrarenal origin."	( Effect of microsomal enzyme activity modulation on N-(3,5-dichlorophenyl)succinimide-induced nephrotoxicity. Brown, PI; Rankin, GO; Richmond, CD; Teets, VJ; Wang, RT; Yang, DJ, 1987)	0.27
" Aspirin, ibuprofen, indomethacin, ketoprofen, flurbiprofen, phenylbutazone, naproxen, prednisolone, and penicillamine did not increase ALA synthase activity and should be safe in porphyria."	( Studies in laboratory animals to assess the safety of anti-inflammatory agents in acute porphyria. McColl, KE; Moore, MR; Thompson, GG, 1987)	0.27
"The physical stability and low blood solubility of the new inhaled anesthetic, I-653, imply that this agent produces limited or no toxic effects."	( Studies of the toxicity of I-653, halothane, and isoflurane in enzyme-induced, hypoxic rats. Eger, EI; Ferrell, LD; Johnson, BH; Strum, DP, 1987)	0.27
"The ability of sulfhydryl compounds to provide protection against the acute toxicity of codeinone, a toxic metabolite of codeine, was investigated in mice."	( Effects of glutathione and phenobarbital on the toxicity of codeinone. Inoue, K; Nagamatsu, K; Terao, T; Toki, S, 1986)	0.57
" If phenobarbital protects from cyclosporine nephrotoxicity because of its enzyme inducing action, it would follow that the parent drug and not a toxic metabolite mediates renal dysfunction."	( Effect of phenobarbital and cimetidine on experimental cyclosporine nephrotoxicity: preliminary observations. Benner, KE; Bennett, WM; Houghton, DC; Sasaki, AW; Schwass, DE, 1986)	1.23
" sex, excess intracranial flow of metrizamide and myelographic blockage were not shown to have a significant influence on the adverse reactions."	( Influence of certain factors on the manifestations of the adverse effects of metrizamide myelography. du Boulay, GH; Paul, E; Yu, YL, 1986)	0.27
"Bicyclic phosphorus esters (BCP) originating from the combustion of fire-retardant polyurethane foam containing phosphorus are highly toxic compounds and potent antagonists of GABA-ergic receptors."	( [Effect of diazepam and phenobarbital on the acute toxicity of bicyclic organophosphorus esters]. Emilianowicz, J; Smok, W, 1986)	0.58
" We assessed the effects of these drugs on the acute toxicity of parathion in rats by measuring the rate of survival at 24 h after the administration of the oral LD50 of parathion to four groups of rats: control and pretreated with the aforementioned drugs."	( Cimetidine enhances and phenobarbital decreases parathion toxicity. Amezcua, JL; Girón, E; Martinez-Tabche, L; Mourelle, M, 1986)	0.58
" These data cannot support the concept that induction of cytochrome P-450 leads to greater formation of the hypothetical toxic metabolite of acetaminophen, or that induction enhances its hepatotoxicity, in the rat."	( Phenobarbital induction does not potentiate hepatotoxicity but accelerates liver cell necrosis from acetaminophen overdose in the rat. Lerche, A; Pedersen, NT; Poulsen, HE, 1985)	1.71
" The intraperitoneal LD50 of lobeline sulfate following SKF 525-A (75 mg/kg), phenobarbital (PB), and 3-methylcholanthrene (3-MC) were 18."	( Effects of SKF 525-A, phenobarbital and 3-methylcholanthrene on the toxicity of lobeline sulfate. Kim, HL, 1985)	0.81
" These results suggest that CMT does not require metabolic activation to produce toxic effects, and that prior exposure to CMT produces tolerance."	( The acute toxicity of cyclopentadienyl manganese tricarbonyl in the rat. Hanzlik, RP; Hogberg, K; Penney, DA; Traiger, GJ, 1985)	0.27
" The higher loading dose was not associated with any short-term adverse effects on cardiorespiratory function, even in spontaneously breathing infants."	( Safety of a higher loading dose of phenobarbital in the term newborn. Donn, SM; Goldstein, GW; Grasela, TH, 1985)	0.55
" It is concluded that ethanol potentiates benzene toxicity by accelerating (1) hydroxylation of benzene, a rate-limiting step of benzene metabolism and (2) transformation of phenol into highly toxic metabolites."	( Effects of ethanol and phenobarbital administration on the metabolism and toxicity of benzene. Nakajima, T; Okuyama, S; Sato, A; Yonekura, I, 1985)	0.58
" The LD50 were determined by the method of moving averages."	( Acute hepatotoxicity and lethality of CCl4 in chlordecone-pretreated rats. Klingensmith, JS; Lockard, V; Mehendale, HM, 1983)	0.27
" The toxic effects were decreased body weight gain, involution of the thymus, increased liver weight, histologic and ultrastructural alterations of the liver, and elevated serum concentrations of aspartate aminotransferase."	( Hepatic tumor-promoting ability of 3,3',4,4',5,5'-hexabromobiphenyl: the interrelationship between toxicity, induction of hepatic microsomal drug metabolizing enzymes, and tumor-promoting ability. Aust, SD; Goodman, JI; Jensen, RK; Sleight, SD; Trosko, JE, 1983)	0.27
" There is experimental evidence that the toxic action of phenytoin lies at the cellular level, predominantly in the cerebellum."	( Side effects of phenobarbital and phenytoin during long-term treatment of epilepsy. Iivanainen, M; Savolainen, H, 1983)	0.61
"Cyclophosphamide (CP) requires metabolic activation for its therapeutic action, and this metabolism results in the formation of two toxic metabolites, acrolein (ACR) and phosphoramide mustard (PM)."	( Biochemical indices of cyclophosphamide-induced lung toxicity. Block, ER; Hood, CI; Patel, JM, 1984)	0.27
" LC was slightly more toxic to control hepatocytes than SC in the graded response range of 10-160 microM."	( Influences of various xenobiotic inducers on cytocidal toxicity of lasiocarpine and senecionine in primary cultures of rat hepatocytes. Cameron, RC; Farber, E; Hayes, MA; Jago, MV; Roberts, E; Safe, SH, 1984)	0.27
" The different toxic effects were related to the structure and metabolism of the compounds."	( The toxic effects in rats of some synthanecine carbamate and phosphate esters analogous to hepatotoxic pyrrolizidine alkaloids. Driver, HE; Mattocks, AR, 1984)	0.27
" The ip LD50 of PC in Swiss male mice was 22 mmol/kg."	( Toxicity of 1-phenylcyclohexene and its interaction with phencyclidine. Berg, IE; Chaturvedi, AK; Choudhuri, MS; Hu, CY; Rao, NG, 1984)	0.27
"Fenitrothion of oral subtoxic dose (100 mg/kg; 4 hr pretreatment) decreased acute oral LD50 of BPMC from 360 to 66 mg/kg in male mice."	( Potentiated toxicity of 2-sec-butylphenyl methylcarbamate (BPMC) by O,O-dimethyl O-(3-methyl-4-nitrophenyl)phosphorothioate (fenitrothion) in mice; relationship between acute toxicity and metabolism of BPMC. Miyaoka, T; Shirasu, Y; Takahashi, H; Tsuda, S, 1984)	0.27
" Single-treatment, subcutaneous LD50 values for DBCP were 102 mg/kg in non-pretreated and 128 mg/kg in phenobarbital pretreated rats."	( Chemical modulation of 1,2-dibromo-3-chloropropane toxicity. Kluwe, WM, )	0.35
"0 g of misonidazole, severe nausea and vomiting are prominent, so that this side effect is a determining factor in the treatment fractionation."	( The role of microsomal enzyme inducers in the reduction of misonidazole neurotoxicity. Bleehen, NM; Jones, DH; Smith, NC; Workman, P, 1983)	0.27
" Serum carbamazepine levels were measured before, during, and, in most cases, after the toxic episodes."	( Carbamazepine--erythromycin interaction leading to carbamazepine toxicity in four epileptic children. Cate, JC; Hedrick, R; Lamb, WA; Morin, R; Williams, F, 1983)	0.27
" The LD50 values at 72, 144, and 168 h for PB-treated rats were approximately 320, 190, and 160 mg/kg, and for eucalyptus treated rats approximately 127, 133, and 133 mg/kg, respectively."	( Effects of microsomal enzyme induction on the toxicity of pyrrolizidine (Senecio) alkaloids. Cheeke, PR; Swick, RA; White, RD, )	0.13
" PRM is a relatively nontoxic anticonvulsant with a different action than PB, and PEMA is both a weak and a relatively toxic anticonvulsant."	( Primidone, phenobarbital, and PEMA: I. Seizure protection, neurotoxicity, and therapeutic index of individual compounds in mice. Bourgeois, BF; Dodson, WE; Ferrendelli, JA, 1983)	0.66
" Treatment of rats with cysteamine prior to treatment with precocene I protected the animals against the toxic effects."	( Metabolism and hepatotoxicity of the naturally occurring benzo[b]pyran precocene I. El-Naggar, SF; Halpin, RA; Jerina, DM; Vyas, KP, 1984)	0.27
" Pretreatment with phenobarbital enhanced the toxic response of renal cortical slices to CHCl3 in vitro as indicated by decreased p-aminohippurate and tetraethylammonium accumulation."	( Mechanism of chloroform nephrotoxicity. IV. Phenobarbital potentiation of in vitro chloroform metabolism and toxicity in rabbit kidneys. Bailie, MB; Hook, JB; Newton, JF; Smith, JH, 1984)	0.86
" Toxic doses of acetylisoniazid and acetylhydrazine, radiolabeled in the acetyl group, were found to bind covalently to liver protein in vivo."	( Isoniazid hepatoxicity: the relationship between covalent binding and metabolism in vivo. Mitchell, JR; Nelson, SD; Snodgrass, WR; Timbrell, JA, 1980)	0.26
"A major consideration which precedes the release of a new chemical into the environment of human beings is the possibility of its producing an undesirable or toxic effect."	( Immunologically mediated toxicity. Amos, HE, 1980)	0.26
"When a compound that is removed from the body by metabolism produces toxicity in extrahepatic organs directly, rather than via active metabolites, induction or inhibition of the drug-metabolizing enzymes simply will decrease or enhance, respectively, the toxic effects of the compound."	( Effects of inducers and inhibitors on drug-metabolizing enzymes and on drug toxicity in extrahepatic tissues. Boyd, MR, 1980)	0.26
"A high proportion of toxic and carcinogenic effects of chemicals develop through the pathway of lethal synthesis."	( The influence of nutrition and inducers on mechanisms of toxicity in humans and animals. McLean, AE; Tame, D; Witts, DJ, 1980)	0.26
"Four alkyl ethers of p-N,N-bis(2-chloroethyl)aminophenol were selected to study the effects of microsomal enzyme induction by phenobarbital on the toxicity changes as reflected by LD50 and alteration of survival times in L-1210 leukemic mice."	( Effects of microsomal enzyme induction on toxicity of p-N, N-bis (2-chloroethyl)aminophenyl alkyl ethers in mice and survival times in L-1210 leukemic mice. Bauguess, CT; Chang, SP; Wynn, JE, 1982)	0.47
" Pulmonary concentrations of unmetabolized 4-ipomeanol were decreased by MC through an increased metabolism of 4-ipomeanol in the liver, primarily to toxic products that bind covalently in that tissue and lead to hepatoxicity."	( Effects of phenobarbital and 3-methylcholanthrene on the in vivo distribution, metabolism and covalent binding of 4-ipomeanol in the rat; implications for target organ toxicity. Boyd, MR; Statham, CN, 1982)	0.65
" These data support the concept that phosgene is the toxic intermediate in chloroform metabolism."	( Effect of cysteine, diethyl maleate, and phenobarbital treatments on the hepatotoxicity of [1H]chloroform. Anders, MW; Stevens, JL, 1981)	0.53
" The LD50 of hymenoxon following carbon tetrachloride pretreatment was increased to 630 +/- 20."	( Toxicity of hymenoxon in Swiss white mice following pretreatment with microsomal enzyme inducers, inhibitors and carbon tetrachloride. Jones, DH; Kim, HL, 1981)	0.26
" Prenatal PB is a practical, effective, and safe method for decreasing the incidence of neonatal hyperbilirubinemia."	( Effectiveness and safety of prenatal phenobarbital for the prevention of neonatal jaundice. Doxiadis, SA; Kipouros, K; Petmezaki, S; Solman, M; Valaes, T, 1980)	0.53
" This study suggests that BZ-3 is not toxic to rats when applied dermally at a dose of 100 mg/kg body wt."	( Safety evaluation of benzophenone-3 after dermal administration in rats. Abdel-Rahman, MS; Barat, SA; Okereke, CS, 1995)	0.29
" The results with PiBx suggest that either the parent compound possesses some direct cytotoxicity or that a toxic metabolite was generated through a biotransformation pathway not inhibited by PiBx."	( 3,5-Dichloroaniline toxicity in Fischer 344 rats pretreated with inhibitors and inducers of cytochrome P450. Brown, PI; Lo, HH; Rankin, GO; Valentovic, MA, 1995)	0.29
" We hypothesized that metabolic activation of MCT by mixed-function oxygenases (MFO) to dehydromonocrotaline (MCTP) is a prerequisite for its immunotoxicity, as has been shown for other toxic effects of MCT."	( Role of metabolism in monocrotaline-induced immunotoxicity in C57BL/6 mice. Buhler, DR; Deyo, JA; Kerkvliet, NI; Reed, RL, )	0.13
" Slices prepared from mice pretreated with phenobarbital (an inducer of P450) potentiated the toxic effects of MPP+."	( Protection and potentiation of 1-methyl-4-phenylpyridinium-induced toxicity by cytochrome P450 inhibitors and inducer may be due to the altered uptake of the toxin. Pai, KS; Ravindranath, V; Sriram, K, 1995)	0.55
" PB pretreatment also enhanced some monitored renal effects of a toxic dose (0."	( Effect of microsomal enzyme modulators on N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS)-induced nephrotoxicity in the Fischer 344 rat. Anestis, DK; Beers, KW; Brown, PI; Nicoll, DW; Rankin, GO, 1993)	0.29
" Intracellular lactate dehydrogenase activity, free calcium levels ([Ca2+]i), reduced glutathione (GSH) and lipid peroxidation were investigated to evaluate the toxic effect of cocaine on hepatocytes."	( Cocaine hepatotoxicity: two different toxicity mechanisms for phenobarbital-induced and non-induced rat hepatocytes. Castell, JV; Gómez-Lechón, J; Jover, R; Ponsoda, X, 1993)	0.53
" Our results suggest that at least P450IIB1-dependent metabolism of OTA leads to its detoxication and that OTA itself may be toxic in some circumstances or that other pathways are responsible for its activation."	( Effect of cytochrome P450 induction on the metabolism and toxicity of ochratoxin A. Gelboin, HV; Omar, RF; Rahimtula, AD, 1996)	0.29
" Adverse effects of antiepileptic treatment may affect the patient's quality of life to an even greater extent than the occurrence of seizures."	( Adverse effects of established and new antiepileptic drugs: an attempted comparison. Gram, L; Rogvi-Hansen, B, 1995)	0.29
" The viability of the outer hair cells did not decrease after the incubation in non-metabolized cisplatin solutions or S9 fraction only, demonstrating the absence of toxic effect from non-metabolized cisplatin and the absence of intrinsic toxic substances in S9 fraction."	( Cisplatin metabolites and their toxicity on isolated cochlear outer hair cells in vitro. Manabe, Y; Saito, H; Saito, T; Yamada, T; Yamamoto, T, 1996)	0.29
" In this study, we orally dosed rats with twice the LD50 of metaldehyde following no pretreatment (control) or pretreatment with 1 of 3 different cytochrome P-450 inducers either phenobarbital or o,p'-DDD (inducers of cytochromes P-450 IIB and IIIA) or 3-methylcholanthrene (an inducer of P-450 IA)."	( Phenobarbital-type P-450 inducers protect rats against metaldehyde toxicity. de Saqui-Sannes, P; Fargier, C; Petit, C; Tardieu, D; Thouvenot, N, 1996)	1.93
"The sea nettle jellyfish toxin (SNTX), which contains several polypeptides, was highly toxic to human hepatocytes."	( Toxicity of sea nettle toxin to human hepatocytes and the protective effects of phosphorylating and alkylating agents. Burnett, JW; Cao, CJ; Eldefrawi, AT; Eldefrawi, ME; Menking, DE; Mioduszewski, RJ; Valdes, JJ, 1998)	0.3
" PB was also the most toxic drug, followed by CBZ and by PHT."	( Anticonvulsant and neurotoxic effects of intracerebroventricular injection of phenytoin, phenobarbital and carbamazepine in an amygdala-kindling model of epilepsy in the rat. Alós, M; Barcia, JA; Belda, V; Rubio, P; Serralta, A, 1999)	0.53
"Doxorubicin is an effective anticancer agent that is limited by numerous adverse effects, cardiotoxicity causing the most concern."	( Inhibition of aldo-keto reductases by phenobarbital alters metabolism, pharmacokinetics and toxicity of doxorubicin in rats. Behnia, K; Boroujerdi, M, 1999)	0.57
" In this study, we examined the anticonvulsant and adverse effects of the three clinically established AEDs carbamazepine (CBZ), phenobarbital (PB), and valproate (VPA) once per month in the same two groups of amygdala-kindled rats over a period of 9 (group 1) or 6 (group 2) consecutive months."	( Repeated acute testing of anticonvulsant drugs in amygdala kindled rats: increase in anticonvulsant but decrease in adverse effect potential. Fiedler, M; Löscher, W, 2000)	0.51
"These data demonstrate that repeated use of the same kindled rats for acute drug testing significantly alters the sensitivity of the animals to the anticonvulsant and adverse effects of drugs."	( Repeated acute testing of anticonvulsant drugs in amygdala kindled rats: increase in anticonvulsant but decrease in adverse effect potential. Fiedler, M; Löscher, W, 2000)	0.31
" Realisation of toxic effects of acrylamide may involve a decrease of the carbohydrate energy metabolism, but in the intact organism these processes precede the induction of the phenobarbital-dependent cytochrome P450."	( [Participation of the cytochrome P450-dependent biotransformation system in realizing the toxic effects of acrylamide]. Romanova, TA, )	0.32
"We report on the effect that pretreating patients with phenobarbital has on averting adverse events when primidone is introduced."	( The "forgotten" cross-tolerance between phenobarbital and primidone: it can prevent acute primidone-related toxicity. Frey, M; Kanner, AM; Parra, J, 2000)	0.82
" The primidone dose was then increased by 125 to 250 mg every 3 weeks until adverse events or a seizure-free state was reached."	( The "forgotten" cross-tolerance between phenobarbital and primidone: it can prevent acute primidone-related toxicity. Frey, M; Kanner, AM; Parra, J, 2000)	0.57
"Twenty-six patients (87%) tolerated the introduction of primidone with minimal or no adverse events."	( The "forgotten" cross-tolerance between phenobarbital and primidone: it can prevent acute primidone-related toxicity. Frey, M; Kanner, AM; Parra, J, 2000)	0.57
"Pretreatment with phenobarbital can minimize the occurrence of intolerable adverse events associated with the introduction of primidone."	( The "forgotten" cross-tolerance between phenobarbital and primidone: it can prevent acute primidone-related toxicity. Frey, M; Kanner, AM; Parra, J, 2000)	0.91
" However, on rare occasions, they can progress to more severe cutaneous disorders, including Stevens-Johnson syndrome and toxic epidermal necrolysis."	( Therapeutic safety monitoring: what to look for and when to look for it. Harden, CL, 2000)	0.31
" The diagnosis was established as the neuro-allergic Adverse Event Following DPT + Polio Immunisation."	( [A severe adverse event after vaccine for diphtheria, tetanus, pertussis and poliomyelitis (DTP + polio) in a 4.5 month old infant]. Balcerska, A; Borzych, D; Irga, N; Wierzba, J, 2000)	0.31
" At equimolar concentrations (1 mM) BHT was the most toxic of the three compounds, causing an 80% decrease in cell viability over a 6 h incubation period."	( Comparative metabolism, covalent binding and toxicity of BHT congeners in rat liver slices. Fujiwara, H; Reed, M; Thompson, DC, 2001)	0.31
" These results suggest an innovative therapeutic approach for treating the adverse effects of acetaminophen and potentially other hepatotoxic agents."	( Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR. Chua, SS; Huang, W; Moore, DD; Wei, P; Zhang, J, 2002)	0.31
"Clinical pharmacologists, neurologists, internists, and all health care givers must consider the efficacy, safety, and side effect profile of a given antiepileptic drug (AED) when determining which drug is best for a given patient."	( Clinical pharmacology of topiramate versus lamotrigine versus phenobarbital: comparison of efficacy and side effects using odds ratios. Claycamp, HG; Lathers, CM; Schraeder, PL, 2003)	0.56
" All patients were effectively treated with no serious adverse events."	( Oral phenobarbital loading: a safe and effective method of withdrawing patients with headache from butalbital compounds. Biondi, D; Loder, E, 2003)	0.83
" Investigations ruled out an infectious etiology; an adverse event following phenobarbital administration was considered."	( Anticonvulsant hypersensitivity syndrome: lymphocyte toxicity assay for the confirmation of diagnosis and risk assessment. Bavdekar, SB; Gogtay, NJ; Kantharia, V; Kshirsagar, NA; Muranjan, MN, 2004)	0.55
" The mechanism proposed for AHS is accumulation of toxic arene oxide metabolites due to a defect in epoxide hydrolase-mediated detoxification."	( Anticonvulsant hypersensitivity syndrome: lymphocyte toxicity assay for the confirmation of diagnosis and risk assessment. Bavdekar, SB; Gogtay, NJ; Kantharia, V; Kshirsagar, NA; Muranjan, MN, 2004)	0.32
" FDVE-mercapturic acid sulfoxides were more toxic than other FDVE conjugates to renal proximal tubular cells in culture."	( Role of cytochrome P4503A in cysteine S-conjugates sulfoxidation and the nephrotoxicity of the sevoflurane degradation product fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A) in rats. Altuntas, TG; Kharasch, ED; Liggitt, HD; Schroeder, JL; Sheffels, P, 2004)	0.32
" minnesota Re 595, a mutant containing only the lipid A and 2-keto-3-deoxyoctonate moiety of the endotoxin molecule, exhibited the same capability to enhance the toxic action of 6-MP."	( Enhanced toxicity for mice of 6-mercaptopurine with bacterial endotoxin. Bradley, SG; Marecki, NM, 1974)	0.25
"Some of the more striking expressions of toxicity are the tremors and seizures observed approximately 100 min after exposure of rats to an acutely toxic dose of acrylonitrile (AN)."	( Effect of cytochrome P450 inhibitors and anticonvulsants on the acute toxicity of acrylonitrile. Benz, FW; Nerland, DE, 2005)	0.33
" Although not acutely toxic at low concentrations (1-20 ng/g), AFB1 had significant chronic effects, including protracted development, increased mortality, decreased pupation rate, and reduced pupal weight."	( Toxicity of aflatoxin B1 to Helicoverpa zea and bioactivation by cytochrome P450 monooxygenases. Berenbaum, MR; Niu, G; Schuler, MA; Wen, Z; Zeng, RS, 2006)	0.33
"Methoxyflurane nephrotoxicity results from biotransformation; inorganic fluoride is a toxic metabolite."	( New insights into the mechanism of methoxyflurane nephrotoxicity and implications for anesthetic development (part 1): Identification of the nephrotoxic metabolic pathway. Kharasch, ED; Liggitt, HD; Park, SB; Schroeder, JL; Sheffels, P; Whittington, D, 2006)	0.33
" Phenobarbital increases in methoxyflurane toxicity do not seem attributable to methoxyflurane dechlorination, MDFA toxicity, or MDFA metabolism to another toxic metabolite, suggesting that nephrotoxicity is attributable to methoxyflurane O-demethylation."	( New insights into the mechanism of methoxyflurane nephrotoxicity and implications for anesthetic development (part 1): Identification of the nephrotoxic metabolic pathway. Kharasch, ED; Liggitt, HD; Park, SB; Schroeder, JL; Sheffels, P; Whittington, D, 2006)	1.24
" Phenobarbital, Aroclor 1254 and beta-naphthoflavone (indirect toxic mechanism) enhanced thyroidal radioiodide accumulation, and the administration of potassium perchlorate had no effect on thyroid: blood (125)I ratio."	( Standardization of the perchlorate discharge assay for thyroid toxicity testing in rats. Coelho-Palermo Cunha, G; van Ravenzwaay, B, 2007)	1.25
"Idiosyncratic hepatotoxicity is a well-known complication associated with aromatic antiepileptic drugs (AAED), and it has been suggested to occur due to the accumulation of toxic arene oxide metabolites."	( Aromatic antiepileptic drugs and mitochondrial toxicity: effects on mitochondria isolated from rat liver. Curti, C; Martins, NM; Medina, WS; Mingatto, FE; Santos, AC; Santos, NA, 2008)	0.35
" However, the clinical use of these drugs is limited by several adverse effects, mainly idiosyncratic hepatotoxicity."	( Involvement of oxidative stress in the hepatotoxicity induced by aromatic antiepileptic drugs. Curti, C; Martins, NM; Medina, WS; Rodrigues, MA; Santos, AC; Santos, NA, 2008)	0.35
" Well-known toxic effects of PB on the liver and thyroid were observed in a dose-dependent manner, along with altered lipid, glucose, and electrolyte metabolism."	( Multiple organ toxicity, including hypochromic anemia, following repeated dose oral administration of phenobarbital (PB) in rats. Enomoto, A; Harada, T; Ishizuka, K; Kawakatsu, H; Kojima, S; Kosaka, T; Nakashima, N; Saka, M; Sasaki, J; Tomita, M; Yoshida, T, 2009)	0.57
" Adverse effects were found in seven of 13 patients."	( Effectiveness and safety of non-intravenous high-dose phenobarbital therapy for intractable epilepsy during childhood. Hamano, S; Ida, H; Kikuchi, K; Koichihara, R; Minamitani, M; Oritsu, T; Tanaka, M, 2011)	0.62
" Our work showed that adverse effects in epileptics under high doses of AVP was related to the association of the AVP with other antiepileptic in particular carbamazépine, phenobarbital and benzodiazepines rather than supra-therapeutic plasmatic concentrations of AVP."	( [Relationship between plasma concentrations of valproic acid and hepatotoxicity in patients receiving high doses]. Atheymen, R; Ben Mahmoud, L; Ghozzi, H; Hakim, A; Hammami, S; Sahnoun, Z; Zeghal, K, )	0.33
" For studies of toxic processes, 1H NMR spectroscopy of biofluids allows monitoring of endogenous metabolite profiles that alter characteristically in response to changes in physiological status."	( A 1H NMR-based metabolomics approach for mechanistic insight into acetaminophen-induced hepatotoxicity. Ando, Y; Fukuhara, K; Ohno, A; Okuda, H; Yamoto, T, 2011)	0.37
"In recent years, phenobarbital, as an antiepileptic drug, has become less popular based on adverse events, especially cognitive and behavioural side effects."	( Side effects of phenobarbital in epilepsy: a systematic review. Li, YP; Zeng, LN; Zhang, LL, 2011)	1.05
" The determination of adverse effects of combined antiepileptic drugs (AEDs) from different studies was complicated by numerous factors including study design, different descriptions of adverse events and a lack of standardised data collection."	( Side effects of phenobarbital in epilepsy: a systematic review. Li, YP; Zeng, LN; Zhang, LL, 2011)	0.72
"Phenobarbital was associated with a higher rate of drug withdrawal although there was no evidence to suggest that phenobarbital caused more adverse events compared to carbamazepine, valproic acid or phenytoin."	( Side effects of phenobarbital in epilepsy: a systematic review. Li, YP; Zeng, LN; Zhang, LL, 2011)	2.16
" The adverse events were assessed as well."	( [A multicenter randomized controlled study on the efficacy and safety of Yinzhihuang oral solution for the treatment of neonatal indirect hyperbilirubinemia in term newborn infants]. , 2011)	0.37
" However, there is limited data on safe and effective detoxification protocols for benzodiazepine-dependent patients."	( Safety and effectiveness of a fixed-dose phenobarbital protocol for inpatient benzodiazepine detoxification. Jacapraro, JS; Kawasaki, SS; Rastegar, DA, 2012)	0.64
" However, these medications have several well-known adverse effects."	( Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children: a randomised trial. Ashrafi, MR; Bavarian, B; Ghaempanah, M; Khosroshahi, N; Malamiri, RA; Nikkhah, A, 2012)	0.62
"Despite rigorous preclinical and clinical safety evaluation, adverse cardiac effects remain a leading cause of drug attrition and post-approval drug withdrawal."	( The role of the anaesthetised guinea-pig in the preclinical cardiac safety evaluation of drug candidate compounds. Borland, S; Ewart, L; Kirk, S; Lainée, P; Marks, L; Philp, K; Skinner, M; Valentin, JP, 2012)	0.38
" VPA was well tolerated and only 47 people reported adverse events which were mostly mild."	( Sodium valproate for epilepsy in rural China: an efficacy and safety assessment in primary care. Li, S; Ru, X; Sander, JW; Wang, W; Wu, J; Zheng, J; Zhu, S, 2012)	0.38
" Suspected adverse effects were seen in only one patient, who developed a transient bradycardia."	( Efficacy and safety of lidocaine for treatment of neonatal seizures. Ågren, J; Flink, R; Hellström-Westas, L; Lundqvist, M; Wickström, R, 2013)	0.39
"Lidocaine has a moderate efficacy as second-line therapy following benzodiazepines for treating neonatal seizures and is not frequently associated with cardiovascular adverse effects."	( Efficacy and safety of lidocaine for treatment of neonatal seizures. Ågren, J; Flink, R; Hellström-Westas, L; Lundqvist, M; Wickström, R, 2013)	0.39
" The frequency of adverse events including somnolence/sedation, polydipsia and increased appetite was significantly higher in the phenobarbital group."	( Clinical efficacy and safety of imepitoin in comparison with phenobarbital for the control of idiopathic epilepsy in dogs. de Vries, F; Keefe, TJ; Löscher, W; Rundfeldt, C; Tipold, A, 2015)	0.86
"The toxicological relevance of effects observed at molecular stage, which occur at dose levels well below classical no-observed adverse effect levels is currently subject to controversial scientific debate."	( Hepatotoxic effects of (tri)azole fungicides in a broad dose range. Haider, W; Heise, T; Knebel, C; Kneuer, C; Marx-Stoelting, P; Niemann, L; Pfeil, R; Rieke, S; Schmidt, F, 2015)	0.42
" Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings."	( Medication side effects among people with epilepsy taking phenobarbital in Zambia. Birbeck, GL; Bui, E; Elafros, MA, 2014)	0.94
"This study explored the adverse effect (AE) profile of phenobarbital (PB) among patients with active convulsive epilepsy (ACE) from resource-poor areas."	( A preliminary observation of the adverse effects of phenobarbital among patients with convulsive epilepsy in rural West China. Chen, D; Chen, T; Deng, Y; He, J; He, L; Li, Y; Liu, L; Mu, J; Si, Y; Tian, L; Zhou, D, 2016)	0.93
" Clinical examination was performed for every patient, and seizure number, antiepileptic medication, and adverse events were detailed at every visit."	( Efficacy and safety of levetiracetam in the management of seizures in neonates. Asadi, F; Moradian, M; Moradian, N; Sedighi, M; Vakiliamini, M, 2016)	0.43
" The content includes dose-related adverse effects, idiosyncratic reactions, behavioural and psychiatric comorbidities, chronic problems, enzyme induction and teratogenesis."	( Tolerability and Safety of Commonly Used Antiepileptic Drugs in Adolescents and Adults: A Clinician's Overview. Brodie, MJ, 2017)	0.46
" These results raise the possibility that the phenobarbital-induced adverse effects could be reduced by a co-treatment with caffeine."	( Caffeine Protects Against Anticonvulsant-Induced Neurotoxicity in the Developing Rat Brain. Bendix, I; Bührer, C; Endesfelder, S; Schiller, C; Sifringer, M; Weichelt, U, 2017)	0.71
" At 42 h of age, the serum PB concentration was in the toxic range at 131 mg/L."	( The Use of Peritoneal Dialysis in Phenobarbitone Toxicity in a Critically Unwell Neonate. Graudins, A; Johnstone, LM; Le Page, AK; Roehr, CC; Stewart, AE, 2018)	0.48
" We propose the use of symptom-triggered phenobarbital for the treatment of AWS as a safe alternative to benzodiazepines."	( The Safety and Utility of Phenobarbital Use for the Treatment of Severe Alcohol Withdrawal Syndrome in the Medical Intensive Care Unit. Cleven, KL; Healy, L; Koenig, S; Kohn, N; Mayo, PH; Narasimhan, M; Oks, M; Wei, M, 2020)	1.12
"Sole use of phenobarbital use for control of AWS may be a safe alternative to benzodiazepines."	( The Safety and Utility of Phenobarbital Use for the Treatment of Severe Alcohol Withdrawal Syndrome in the Medical Intensive Care Unit. Cleven, KL; Healy, L; Koenig, S; Kohn, N; Mayo, PH; Narasimhan, M; Oks, M; Wei, M, 2020)	1.24
"This study evaluated the relationship between blood concentration of phenobarbital (PB) and its efficacy as well as adverse events in people with epilepsy in rural China."	( Blood concentration, efficacy, and adverse events of phenobarbital: A prospective study in rural China. Ding, D; Hong, Z; Sun, W; Wang, J; Wang, T; Zhang, Q, 2019)	1
"The study objective was to investigate the prevalence and clinical characteristics of phenobarbitone-associated adverse effects in epileptic cats."	( Prevalence and clinical characteristics of phenobarbitone-associated adverse effects in epileptic cats. Corsini, G; De Risio, L; Gutierrez-Quintana, R; Marsh, O; Van Dijk, J, 2021)	0.62
"The medical records of two veterinary referral clinics from 2007 to 2017 were searched for cats fulfilling the inclusion criteria of a diagnosis of epilepsy, treatment with phenobarbitone and available follow-up information on the occurrence of adverse effects."	( Prevalence and clinical characteristics of phenobarbitone-associated adverse effects in epileptic cats. Corsini, G; De Risio, L; Gutierrez-Quintana, R; Marsh, O; Van Dijk, J, 2021)	0.62
" One or more of the following adverse effects were reported in 47% of the cats: sedation (89%); ataxia (53%); polyphagia (22%); polydipsia (6%); polyuria (6%); and anorexia (6%)."	( Prevalence and clinical characteristics of phenobarbitone-associated adverse effects in epileptic cats. Corsini, G; De Risio, L; Gutierrez-Quintana, R; Marsh, O; Van Dijk, J, 2021)	0.62
"The prevalence of phenobarbitone-associated adverse effects was 47%."	( Prevalence and clinical characteristics of phenobarbitone-associated adverse effects in epileptic cats. Corsini, G; De Risio, L; Gutierrez-Quintana, R; Marsh, O; Van Dijk, J, 2021)	0.62
"Phenobarbitone is at least as efficacious and safe as other drugs like phenytoin and levetiracetam."	( Efficacy and Safety of Phenobarbitone as First-Line Treatment for Neonatal Seizure: A Systematic Review and Meta-Analysis. Kumar, J; Meena, J; Saini, L; Yadav, J, 2021)	0.62
"previous studies have shown that phenobarbital (PB) is a effective and safe drug in the treatment of benign convulsions with mild gastroenteritis (CwG), but there is a lack of large sample prospective randomized controlled study of different doses."	( Efficacy and safety of phenobarbital for benign convulsions with mild gastroenteritis: A prospective randomized controlled study. Chen, H; Chen, Y; Xie, J; Yi, Z; Yu, X; Zha, J; Zhong, J, 2022)	1.31
" Drowsiness was the most frequent adverse reaction."	( Efficacy and safety of phenobarbital for benign convulsions with mild gastroenteritis: A prospective randomized controlled study. Chen, H; Chen, Y; Xie, J; Yi, Z; Yu, X; Zha, J; Zhong, J, 2022)	1.03

Pharmacokinetics

The effects of pretreatment with the enzyme inducers, phenobarbital (PB) and 3-methylcholanthrene (3-MC), on the pharmacokinetic and pharmacodynamic parameters of bumetanide were examined in rats. Oral administration of multiple doses of activated charcoal significantly decreased the serum half-life and AUC.

Excerpt	Reference	Relevance
" The half-life of PB is twice that of PRM and PEMA."	( Single-dose pharmacokinetics and anticonvulsant efficacy of primidone in mice. Friel, PN; Leal, KW; Rapport, RL; Wilensky, AJ, 1979)	0.26
" The overall elimination rate constant for loss of phenobarbital from serum, Kel, was significantly reduced after repeated doses, and Cmax infinity values calculated from single-dose data poorly predicted observed Cmax infinity values."	( Pharmacokinetics of phenobarbital following single and repeated doses. Booker, HE; Viswanathan, CT; Welling, PG, )	0.71
" However, the apparent elimination half-life (t 1/2) for MIS was reduced by 20-67%, and the area under the curve (AUC) was decreased by 23-49% in plasma, brain and tumour."	( Effects of pretreatment with phenobarbitone and phenytoin on the pharmacokinetics and toxicity of phenytoin on the pharmacokinetics and toxicity of misonidazole in mice. Workman, P, 1979)	0.26
" Primidone was rapidly absorbed, so that maximal serum concentrations were reached after 2 hr, the concentration fell then with a half-life averaging 5 hr in Beagles and 10 hr in Mongrels."	( Pharmacokinetics of primidone and its active metabolites in the dog. Frey, HH; Göbel, W; Löscher, W, 1979)	0.26
"A few conclusive experimental models (barbiturate sleep, tetrabenazine reversion, maximum electroshock) were chosen to collect comprehensive data on the pharmacodynamic characteristics of amitriptylinoxide."	( Special experiments on central nervous effects of amitriptylinoxide considering pharmacokinetic aspects. Wenzl, H, 1978)	0.26
" It was possible to calculate the pharmacokinetic parameters using a two compartment open model."	( Pharmacokinetics of phenobarbital in childhood. Gladtke, E; Heimann, G, 1977)	0.58
" A pharmacokinetic model with an exponentially increasing elimination rate term was used to describe the data."	( Phenobarbital pharmacokinetics in neonates. Painter, M; Pippenger, C; Pitlick, W, 1978)	1.7
"Anticonvulsant therapy was among the first areas to benefit from clinical pharmacokinetic studies."	( Clinical pharmacokinetics of anticonvulsants. Dam, M; Hvidberg, EF, 1976)	0.26
" In the experimental condition where PB decreases the activity of CPA, serum levels of CPA, assayed by means of a new specific gas-chromatographic method, and of its NBP-alkylating metabolites, indicate that this effect may be explained on a pure pharmacokinetic basis."	( Effect of phenobarbital on cyclophosphamide cytotoxic activity and pharmacokinetics in mice. Bossi, A; Colombo, T; Donelli, MG; Garattini, S; Pantarotto, C; Sironi, M; Spreafico, F; Vecchi, A, )	0.53
" 2 Pharmacokinetic assessment of the data indicated no significant intra-subject changes in kinetic parameters before or after chronic treatment with ephedrine HCl (11 mg three times a day) alone or in combination."	( The pharmacokinetics of ephedrine after oral dosage in asthmatics receiving acute and chronic treatment. May, CS; Paterson, JW; Pickup, ME; Ssendagire, R, 1976)	0.26
" Pharmacokinetic parameters and enzyme kinetic data both in normal and in tumor-bearing animals will be presented."	( Importance of pharmacokinetic studies on cyclophosphamide (NSC-26271) in understanding its cytotoxic effect. Bartosek, I; Colombo, T; Donelli, MG; Guaitani, A; Martini, A; Modica, R; Pacciarini, MA, 1976)	0.26
" The effects of other antiepileptics on the serum protein binding, erythrocyte distribution and metabolism of ZNS were also studied in vitro to elucidate the mechanism of pharmacokinetic interaction of ZNS."	( Pharmacokinetic interaction of zonisamide in rats. Effect of other antiepileptics on zonisamide. Fukuchi, H; Kimura, M; Kimura, Y; Kitaura, T; Miyake, K; Tanaka, N, 1992)	0.28
"The effect of Chinese herbal medicines (Huan Shao Tan and Pu Chung Yi Chi Tang) and western drugs (sodium phenobarbital and cimetidine) on the serum concentration and pharmacokinetic parameters of theophylline and cytochrome P-450 of Sprague-Dawley (SD) rats of three different ages were examined."	( Effect of traditional Chinese herbal medicines on the pharmacokinetics of western drugs in Sprague-Dawley rats of different ages (II): Aminophylline-huan shao tan and aminophylline-pu chung yi chi tang. Chen, SM; Hou, SJ; Lin, SY; Perng, RI; Young, TK, 1992)	0.5
"Routine clinical pharmacokinetic data collected from patients receiving phenobarbitone have been analysed to evaluate the role of patient characteristics for estimating dosing regimens."	( Phenobarbitone population pharmacokinetics from routine clinical data: role of patient characteristics for estimating dosing regimens. Aoyama, T; Higuchi, S; Yukawa, E, 1992)	0.28
" Although no significant differences between the strains were seen in the pharmacokinetics of cocaine, the half-life of both norcocaine and N-hydroxynorcocaine was significantly longer in DBA mice."	( Pharmacokinetic analysis of the metabolism of cocaine to norcocaine and N-hydroxynorcocaine in mice. Boyer, CS; Petersen, DR, )	0.13
" Pharmacokinetic dose prediction methods have been developed allowing individual dosage adaptation."	( Therapeutic drug monitoring and pharmacokinetic dose prediction methods. Oellerich, M, 1992)	0.28
" Mean kinetic variables after single and repeated orally administered doses (42 days) were: elimination half-life = 24."	( Pharmacokinetics of phenobarbital in horses after single and repeated oral administration of the drug. Knox, DA; Krista, LM; Nostrandt, AC; Pedersoli, WM; Ravis, WR; Schumacher, J; Spano, JS, 1992)	0.61
"74 L/h) and elimination half-life of 61h were determined."	( Phenobarbital pharmacokinetics in obesity. A case report. Danziger, LH; Rodvold, KA; Wilkes, L, 1992)	1.73
"A possible pharmacokinetic interaction between teniposide and anticonvulsant medications was evaluated in pediatric patients."	( Increased teniposide clearance with concomitant anticonvulsant therapy. Baker, DK; Christensen, ML; Evans, WE; Pui, CH; Relling, MV; Rodman, JH, 1992)	0.28
" The pharmacokinetic parameters of this metabolite (PB) were determined in guinea-pigs, and their identity with the pharmacokinetic parameters of PB as the parent drug was confirmed."	( Use of normal-phase microcolumn high-performance liquid chromatography for the study of hydrolytic stability, metabolic profiling and pharmacokinetics of an antiepileptic drug, benzonal. Chankvetadze, BG; Okujava, VM; Rogava, MM; Rukhadze, MD; Tkesheliadze, NB, 1991)	0.28
"The effects of pretreatment with the enzyme inducers, phenobarbital (PB) and 3-methylcholanthrene (3-MC), on the pharmacokinetic and pharmacodynamic parameters of bumetanide were examined in rats."	( Effects of phenobarbital and 3-methylcholanthrene pretreatment on the pharmacokinetics and the pharmacodynamics of bumetanide in rats. Choi, YM; Jang, SH; Lee, MG; Lee, SH, 1991)	0.92
" One subject showed an atypical pharmacokinetic profile, characterized by relatively high levels of MMP and a delayed appearance of low levels of PB."	( Comparative pharmacokinetics and pharmacodynamics of eterobarbital and phenobarbital in normal volunteers. Barzaghi, N; Galimberti, CA; Gatti, G; Manni, R; Perucca, E; Tartara, A; Zucca, C, )	0.36
"The effects of pretreatment with the enzyme inducers phenobarbital (PB) and 3-methylcholanthrene (3-MC) on the pharmacokinetic and pharmacodynamic parameters of furosemide were examined in rats."	( Effects of phenobarbital and 3-methylcholanthrene pretreatment on the pharmacokinetics and pharmacodynamics of furosemide in rats. Choi, YM; Kim, SH; Lee, MG, 1991)	0.92
"The in vivo N-demethylation of (+) and (-)3,4-methylenedioxymethamphetamine (MDMA) to 3,4-methylenedioxyamphetamine (MDA) was determined and the pharmacokinetic relationship between the two compounds calculated."	( Stereochemical differences in the metabolism of 3,4-methylenedioxymethamphetamine in vivo and in vitro: a pharmacokinetic analysis. Chang, AS; Cho, AK; Distefano, EW; Hiramatsu, M; Jenden, DJ, )	0.13
" The elimination half-life (t1/2 b) after the final day of treatment was 43."	( Pharmacokinetics of phenobarbital in the cat following multiple oral administration. Allen, DG; Black, WD; Cochrane, SM; Lumsden, JH; Parent, JM, 1990)	0.6
" In addition to physiologic factors, such as blood pressure and cerebral blood flow, pharmacokinetic principles, including half-life, distribution, elimination, and volume of distribution (with special regard to an agent's lipid-solubility rating), should be applied."	( The pharmacokinetics of agents used to treat status epilepticus. Browne, TR, 1990)	0.28
" Pharmacodynamic effects were quantitated after 2 weeks of treatment."	( Pharmacodynamics of tolerance development to the anesthetic and anticonvulsant effects of phenobarbital in rats. Danhof, M; Dingemanse, J; Hameter, BM, 1990)	0.5
" An antipyrine pharmacokinetic and impedance analysis of 15 healthy male subjects was performed before and on the 14th day of phenobarbital administration (i."	( Bioimpedance assessment of antipyrine pharmacokinetics before and after enzyme induction. Peterson, EL; Pilla, AM; Popovich, J; Svensson, CK; Zarowitz, BJ, 1990)	0.49
"There is considerable evidence of gender differences in the pharmacokinetics of numerous drugs, particularly in rodents, but very limited information concerning the effect of gender on pharmacodynamic characteristics (concentration-activity relationships)."	( Gender differences in the pharmacodynamics of barbiturates in rats. Hoffman, A; Levy, G, 1989)	0.28
"The relationship between the serum concentration of phenobarbital and its pharmacodynamic effects was assessed in a double-blind controlled study in eight normal volunteers who were given single oral doses of phenobarbital (200 mg) and placebo according to a randomized cross-over design."	( Time-dependent pharmacodynamic effects of phenobarbital in humans. Barzaghi, N; Galimberti, CA; Gatti, G; Manni, R; Perucca, E; Tartara, A; Zucca, C, 1989)	0.79
"The present study shows the absence of in vivo pharmacokinetic isotope effect on phenobarbitone (PB) C5-ethyl deuteration (PBd5) following oral administration to man of equimolar PB/PBd5 mixtures (0."	( Pharmacokinetic equivalence of 5(ethyl(2H)5)- and unlabelled phenobarbitone. Benchekroun, Y; Brazier, JL; Cherrah, Y; Falconnet, JB; Ribon, B, 1989)	0.28
" The pharmacokinetics of phenobarbital were studied in a separate set of rats (elimination half-life 11 +/- 2 hr)."	( Pharmacokinetic modeling of the anticonvulsant action of phenobarbital in rats. Danhof, M; Dingemanse, J; van Bree, JB, 1989)	0.83
"Phenobarbitone pretreatment has been shown to increase amiodarone total clearance and decrease amiodarone elimination half-life after a single intravenous amiodarone dose in the rat."	( Effect of phenobarbitone on the pharmacokinetics and tissue levels of amiodarone in the rat. Bernhard, R; Ferguson, RK; Fruncillo, RJ; Swanson, BN; Vlasses, PH, 1985)	0.27
" Elimination half-life was 58."	( Pharmacokinetics of phenobarbitone in protein energy malnutrition. Raina, RK; Sharma, DB; Syed, GB, 1986)	0.27
"The influence of progabide, a new antiepileptic drug, on the pharmacokinetic profiles of phenobarbital, phenytoin, carbamazepine, and valproic acid was evaluated in four separate studies, each including six young healthy volunteers."	( Pharmacokinetic interactions of progabide with other antiepileptic drugs. Bianchetti, G; Morselli, PL; Padovani, P; Thénot, JP; Thiercelin, JF, )	0.35
" Inoculation of MMC together with 5-fluorouracil and doxorubicin did not change the terminal half-life of MMC but decreased the total body clearance and the volume of distribution."	( Pharmacokinetics and toxicity of mitomycin C in rodents, given alone, in combination, or after induction of microsomal drug metabolism. Kanyár, B; Kerpel-Fronius, S; Lelieveld, P; Pinedo, HM; Stuurman, M; Verwey, J, 1988)	0.27
" The resultant 14CO2 exhalation rate time profiles have been used to derive a compartmental pharmacokinetic model for the antipyrine breath test in the rat."	( The antipyrine breath test in the rat: a pharmacokinetic model. Chenery, RJ; Lockwood, GF; Norman, SJ; Oldham, HG; Standring, P, )	0.13
"The volatility and lipophilicity by which organic solvents are distinct from other chemicals constitute a characteristic pharmacokinetic feature."	( Pharmacokinetics of organic solvent vapors in relation to their toxicity. Nakajima, T; Sato, A, 1987)	0.27
" and oral results, phenobarbital displayed two-compartment pharmacokinetics in the horse with a terminal half-life of 19."	( A pharmacokinetic study of phenobarbital in mature horses after oral dosing. Duran, SH; Pedersoli, WM; Ravis, WR; Schumacher, J, 1987)	0.9
" Serial venous blood samples (n = 21) were collected from each dog before (base line) and after the administration of phenobarbital sodium for pharmacokinetic evaluation."	( Pharmacokinetics of single doses of phenobarbital given intravenously and orally to dogs. Pedersoli, WM; Ravis, WR; Wike, JS, 1987)	0.76
" This investigation, which was designed to exclude or account for pharmacokinetic variables and to avoid confounding secondary effects, such as hypothermia and development of acute functional tolerance, showed a substantial increase in CNS sensitivity to phenobarbital and ethanol with increasing age in rats between the age of 1 and 9 months, and a less pronounced increase (phenobarbital) or no significant change (ethanol) in rats between 9 and 18 months of age."	( Effect of age on the pharmacodynamics of phenobarbital and ethanol in rats. Levy, G; Wanwimolruk, S, 1987)	0.72
" The mean apparent half-life of phenobarbital estimated in 11 infants was 175."	( Pharmacokinetic basis for antenatal dosing of phenobarbital for the prevention of neonatal intracerebral hemorrhage. Cepeda, EE; Ilagan, N; Kauffman, RE; Shankaran, S, 1986)	0.81
"Stable-isotope tracer methods are described for answering the following questions about a drug: Does the drug exhibit dose-dependent changes in pharmacokinetic properties? What are the drug's Michaelis constant (Km) and maximum velocity (Vmax) for enzymatic biotransformation; Are the dose-dependent pharmacokinetic changes great enough to be clinically important? and Which routes of the drug's biotransformation are responsible for the drug's dose-dependent pharmacokinetic properties? Illustrative data are provided from tracer studies performed with a drug with dose-dependent pharmacokinetic properties, phenytoin, and a drug that does not exhibit dose-dependent pharmacokinetic properties, phenobarbital."	( Pharmacokinetics: dose-dependent changes. Browne, TR; Evans, BA; Evans, JE; Greenblatt, DJ; Schumacher, GE; Szabo, GK, )	0.28
" Oral administration of multiple doses of activated charcoal significantly decreased the serum half-life and AUC (area under the curve) and increased the total body clearance of both theophylline and phenobarbital as compared with their respective controls."	( Accelerated clearance of intravenously administered theophylline and phenobarbital by oral doses of activated charcoal in rats. A possibility of the intestinal dialysis. Arimori, K; Nakano, M, 1986)	0.69
" In general, a two-compartment, steady-state pharmacokinetic model described the uptake data."	( Inhalation pharmacokinetics of 1,2-dichloroethane after different dietary pretreatments of male Sprague-Dawley rats. Igwe, OJ; Que Hee, SS; Wagner, WD, 1986)	0.27
" Based on the available data it seems that one may postulate the following conclusions: (1) that the distribution factors as well as changes in drug elimination capacities seem to play a role, perhaps with differing relative importance, during each of the maturational periods; (2) that the physicochemical properties of a drug and its dosage, as well as changes in the volume of distribution in children, in the course of certain disease states may have a significant effect on kinetics of drug disposition in the body; (3) that systemic clearance, a model independent parameter, rather than elimination half-life, a hybrid pharmacokinetic parameter, more accurately reflects elimination of some drugs from the body; (4) that each drug and every clinical situation may require the evaluation of the direct effect on pharmacokinetic processes, since general principles may not always apply; (5) that drug disposition studies should also be performed, if possible, on patients under actual clinical situations and receiving the usual therapeutic regime, and (6) that the half-life of colistin is independent of postnatal age which should serve as a warning not to generalize about drug excretion in the young infant."	( Clinical pharmacokinetics of changes in drug elimination in children. Prandota, J, 1985)	0.27
" Phenobarbital bolus doses and infusion rates were based on a preliminary pharmacokinetic study (7 rats) and were varied to achieve a broad range of steady state levels."	( Effects of phenobarbital steady state levels on antipyrine clearance and distribution in the rat. Bialer, M; Levy, RH; Pei, YY, )	1.43
"The purpose of this investigation was to determine if the reported prolongation of barbiturate- and ethanol-induced sleeping times by nicotine in rodents are pharmacodynamic or pharmacokinetic interactions."	( Kinetics of drug action in disease states XI: effect of nicotine on the pharmacodynamics and pharmacokinetics of phenobarbital and ethanol in rats. Hisaoka, M; Levy, G, 1985)	0.48
" The results showed rapid increase in plasma concentration after IM injection in 10 of 13 subjects with a peak concentration reached 60 minutes after injection."	( [Pharmacokinetics of injectable phenobarbital in the premature infant. Study of a new lyophilized form]. Brazier, JL; Claris, O; Kossmann, JC; Ribon, B; Salle, B, 1985)	0.55
"Routine clinical pharmacokinetic (PK) data collected from 59 preterm infants who received phenobarbital were analyzed to estimate population PK parameters."	( Neonatal population pharmacokinetics of phenobarbital derived from routine clinical data. Donn, SM; Grasela, TH, 1985)	0.76
" The clearance of both antipyrine and d-propranolol was increased and the half-life decreased significantly by phenobarbital."	( Increased clearance of antipyrine and d-propranolol after phenobarbital treatment in the monkey. Relative contributions of enzyme induction and increased hepatic blood flow. Branch, RA; Nies, AS; Shand, DG; Wilkinson, GR, 1974)	0.71
"0 ml/h/kg of body weight), the elimination half-life (95 h), the elimination rate constant (0."	( Phenobarbital pharmacokinetics and salivary and serum concentrations in pregnancy. Heikkinen, JE; Luoma, PV; Ylöstalo, PR, 1982)	1.71
" Hexobarbital and heptabarbital were chosen for this purpose as model substrates because of their structural, pharmacokinetic as well as metabolic similarity."	( Pharmacokinetics of simultaneously administered hexobarbital and heptabarbital in rats: an alternative approach to metabolic correlation studies. Breimer, DD; Langendijk, PN; van der Graaff, M; Vermeulen, NP, 1983)	0.27
" Pharmacokinetic interactions between antiepileptic drugs may lead to considerable fluctuation in plasma drug concentration, and monotherapy is often preferable."	( Pharmacokinetics of antiepileptic drugs. Neuvonen, PJ; Tokola, RA, 1983)	0.27
" The principal pharmacokinetic parameters of guanfacine were greatly altered, with extended biotransformation and a decrease in the half-life compared to the values observed in other cases of severe renal insufficiency."	( Pharmacokinetic aspects of guanfacine withdrawal syndrome in a hypertensive patient with chronic renal failure. Comoy, E; Fillastre, JP; Godin, M; Guerret, M; Kiechel, JR; Lavene, D, 1983)	0.27
" No correlation between the pharmacodynamic action of phenobarbital and its cerebral level was noted."	( The effect of chlorpromazine on pharmacokinetics and pharmacodynamics of phenobarbital in X-irradiated rats. Godlewski, J; Nowakowska, E; Okulicz-Kozaryn, I; Wójciakowa, Z, )	0.61
"1 micrograms/ml at 1 h after initiation of infusion with a mean (+/- se) half-life of 12."	( Preliminary study on the pharmacokinetics of phenobarbital in the neonatal foal. Hendeles, L; Hill, MR; Mayhew, IG; Spehar, AM, 1984)	0.53
" Whether comparing the absolute or standardized pharmacokinetic data, lean and obese Zucker rats will exhibit 2- to 3-fold higher phenobarbital plasma concentrations after administration of a standard 75- to 100-mg/kg enzyme-inducing regimen relative to Sprague-Dawley rats."	( Phenobarbital in the genetically obese Zucker rat. I. Pharmacokinetics after acute and chronic administration. Blouin, RA; Brouwer, KL; Kostenbauder, HB; McNamara, PJ, 1984)	1.92
" Oxazepam elimination half-life was shorter and apparent oral clearance higher in treated patients than in age and sex matched control subjects."	( Oxazepam pharmacokinetics in patients with epilepsy treated long-term with phenytoin alone or in combination with phenobarbitone. Hawksworth, GM; Khir, AS; Petrie, JC; Scott, AK; Steele, WH, 1983)	0.27
" Postnatal age and gestational age accounted for some of the variability in pharmacokinetic response to chloramphenicol."	( The pharmacokinetics of chloramphenicol in the neonate and young infant. de Louvois, J; Hurley, R; Mulhall, A, 1983)	0.27
"The pharmacokinetic parameters controlling paraldehyde elimination were determined in nine infants infused with paraldehyde at the rate of 150 mg/kg/hr in a 5% solution in 5% dextrose for the treatment of status epilepticus."	( Pharmacokinetics of paraldehyde disposition in the neonate. Boutwell, WC; Gessner, PK; Giacoia, GP; Zaleska, MM, 1984)	0.27
" Thus, the plasma phenobarbital half-life was reduced by 78-88% during haemoperfusion."	( Pharmacokinetic evaluation of haemoperfusion in phenobarbital poisoning. Dahl, T; Enger, E; Jacobsen, D; Lunde, PK; Wiik-Larsen, E, 1984)	0.86
" As expected for a highly cleared drug, enzyme induction had no measurable effect on the terminal half-life of norethindrone in the perfused liver preparation."	( An investigation of the effects of phenobarbitone on the pharmacokinetics of norethindrone in the rat using liver perfusion and everted gut sacs. Back, DJ; Macnee, CM; Orme, ML; Rowe, PH; Smith, E, 1984)	0.27
" This review contains relevant pharmacokinetic data on anticonvulsant drugs widely used during pregnancy and the neonatal period."	( Anticonvulsants during pregnancy and lactation. Transplacental, maternal and neonatal pharmacokinetics. Egger, HJ; Helge, H; Kuhnz, W; Nau, H; Rating, D, )	0.13
" A pharmacokinetic analysis showed that the charcoal decreased the serum half-life of phenobarbital form 110 +/- 8 to 45 +/- 6 hours (S."	( Acceleration of the body clearance of phenobarbital by oral activated charcoal. Berg, MJ; Berlinger, WG; Goldberg, MJ; Johnson, GF; Spector, R, 1982)	0.76
"A physiologically based pharmacokinetic model, which is an extension of the Bischoff-Dedrick multiorgan model, was developed to described the kinetics of barbiturates (hexobarbital, phenobarbital, and thiopental) in the rat."	( Comparative physiologically based pharmacokinetics of hexobarbital, phenobarbital and thiopental in the rat. Awazu, S; Hanano, M; Igari, Y; Sugiyama, Y, 1982)	0.69
" However, its biological half-life and the apparent distribution volume of the central compartment were significantly lower and the intercompartmental transport rate constants and the urinary excretion rate constant were significantly greater, in phenobarbital treated rats than in control rats."	( Effects of phenobarbital on the distribution pharmacokinetics and biological half-lives of model nonmicrosomal enzyme metabolizable sulfonamides in rats. Kundu, S; Nagwekar, JB, 1982)	0.84
" for therapeutic reasons, the elimination kinetics appeared to follow a two-compartment open model, with a significant difference in the therminal plasma half-life between premature (26."	( Pharmacokinetics of furosemide in neonates. Broquaire, M; Legagneur, M; Morselli, PL; Vert, P, 1982)	0.26
" The biological half-life of warfarin and the duration of its anticoagulant effect were reduced substantially by treatment with phenobarbital."	( Comparative pharmacokinetics of coumarin anticoagulants. XLVI: Effect of treatment of phenobarbital on pharmacokinetics of (S)-(-)-warfarin in rats. Levy, G; Slattery, JT; Yacobi, A, 1980)	0.69
" For this and other reasons, at the Hospital Pharmacological Service a clinical pharmacokinetic laboratory was set up about two years ago."	( Clinical pharmacokinetics: the pharmacological monitoring of plasmatic levels in therapy. Bonora, MR; Guaglio, R; Rondanelli, R; Terzoni, PA, 1980)	0.26
"A pharmacokinetic study of phenobarbital labeled with stable (nonradioactive) isotopes [1,3-15N, 2-13C] was conducted in patients undergoing chronic drug treatment for epilepsy."	( Stable isotope methodology and gas chromatography mass spectrometry in a pharmacokinetic study of phenobarbital. Kapetanović, IM; Kupferberg, HJ, 1980)	0.78
"Therapeutic drug monitoring (TDM) of chronic treatments is justified for several reasons, including relative over- or underdosage due to variable individual elimination, pharmacokinetic interactions in drug combinations, and noncompliance."	( Validation of a quick modeling program generating clearance estimates at steady state for routine therapeutic drug monitoring. Alric, R; Beglia, S; el Battah, A, 1995)	0.29
" Pharmacokinetic parameters of phenobarbital and parahydroxyphenobarbital were determined from plasma and urine samples obtained after 28 days of daily administration of 100 mg phenobarbital and after a further 9 days of phenobarbital plus 2400 mg/day felbamate or placebo."	( Effects of felbamate on the pharmacokinetics of phenobarbital. Banfield, CR; Colucci, RD; Glue, P; Guillaume, M; Lin, CC; Meehan, JW; Mojavarian, P; Nezamis, J; Radwanski, E; Reidenberg, P, 1995)	0.83
" The plasma cyclophosphamide disposition data of these patients were fit by a one-compartment pharmacokinetic model, in which the decline of plasma cyclophosphamide concentration after reaching the initial steady state was modeled as being due to an increase in the clearance rate of cyclophosphamide."	( Nonlinear pharmacokinetics of cyclophosphamide in patients with metastatic breast cancer receiving high-dose chemotherapy followed by autologous bone marrow transplantation. Black, KC; Chen, TL; Colvin, OM; Grochow, LB; Kennedy, MJ; Noe, DA; Passos-Coelho, JL, 1995)	0.29
" The possibility of a pharmacodynamic interaction involving neurotransmitters is also discussed."	( Pharmacodynamic and pharmacokinetic interactions between alpha-methylparatyrosine and phenobarbitone. Elhwuegi, AS, 1994)	0.29
"With the introduction of three new anti-epileptic drugs (AEDs) in the UK during the past 4 years as adjunctive add-on therapy, the possibility of AED pharmacokinetic interactions has become a relevant consideration."	( Phenobarbitone to gabapentin: a guide to 82 years of anti-epileptic drug pharmacokinetic interactions. Patsalos, PN, 1994)	0.29
"To report a case of a potential pharmacokinetic interaction between felbamate and phenobarbital in a patient with epilepsy."	( Potential pharmacokinetic interaction between felbamate and phenobarbital. Gidal, BE; Zupanc, ML, 1994)	0.76
" The PB-pretreated rats showed a 6-fold decrease in AUC, a 5-fold decrease in Cmax and an 8-fold increase in CLtot compared to the saline treated controls."	( Effects of phenobarbital and 3-methylcholanthrene pretreatment on the pharmacokinetics of praziquantel in rats. Hasler, JA; Masimirembwa, CM; Naik, YS, )	0.52
" Differential effects on the pharmacodynamic parameters were seen."	( Characterization of the pharmacodynamics of several antiepileptic drugs in a direct cortical stimulation model of anticonvulsant effect in the rat. Danhof, M; Hoogerkamp, A; Vis, PW; Voskuyl, RA, 1994)	0.29
" These results suggest that ZNS has little effect on the pharmacokinetic behaviors of other antiepileptic drugs."	( Pharmacokinetic interaction of zonisamide in rats. Effect of zonisamide on other antiepileptics. Fukuchi, H; Kimura, M; Kimura, Y; Kitaura, T; Miyake, K; Tanaka, N, 1993)	0.29
" These data indicate that pharmacodynamic results obtained with cultured hepatocytes represent a good qualitative and quantitative approximation of the in vivo hepatic responses in male rats caused by PB-type inducers."	( Pharmacodynamics of cytochrome P450 2B induction by phenobarbital, 5-ethyl-5-phenylhydantoin, and 5-ethyl-5-phenyloxazolidinedione in the male rat liver or in cultured rat hepatocytes. Jones, CR; Lubet, RA; Mellini, DW; Nims, RW; Sinclair, JF; Sinclair, PR; Syi, JL; Thomas, PE, )	0.38
" Particular attention has been paid to the role of age in determining the variability of pharmacokinetic parameters, but the effect of other factors, such as different formulations and routes of administration, concomitant treatments, gender and pathological conditions other than epilepsy, have also been considered."	( Clinical pharmacokinetics of antiepileptic drugs in paediatric patients. Part I: Phenobarbital, primidone, valproic acid, ethosuximide and mesuximide. Avanzini, G; Battino, D; Estienne, M, 1995)	0.52
" These values are similar to those previously reported from both traditional and NONMEM pharmacokinetic studies."	( Determination of phenobarbitone population clearance values for South African children. Botha, JH; Gray, AL; Miller, R, 1995)	0.29
" The concentrations for CZX and OH-CZX over time were simultaneously fitted to a model of first-order elimination of CZX and first-order formation and elimination of OH-CZX using the computer program PCNONLIN to give pharmacokinetic parameters."	( Effects of cytochrome P450 2E1 modulators on the pharmacokinetics of chlorzoxazone and 6-hydroxychlorzoxazone in rats. Chen, L; Yang, CS, 1996)	0.29
" A pharmacokinetic model was developed to describe the influence of phenobarbital on the hepatobiliary disposition of VPA and valproate glucuronide (V-G) in the IPL; all processes governing VPA and V-G disposition appeared to be linear."	( Hepatobiliary disposition of valproic acid and valproate glucuronide: use of a pharmacokinetic model to examine the rate-limiting steps and potential sites of drug interactions. Booth, CL; Brouwer, KL; Pollack, GM, 1996)	0.53
" To prepare O6-benzylguanine for clinical trials and to determine the availability and disposition of O6-benzyl-7,8-dihydro-8-oxoguanine (O6-benzyl-8-oxoguanine), its major metabolite, pharmacokinetic parameters of these compounds were investigated in male Sprague-Dawley rats."	( Pharmacokinetics of O6-benzylguanine in rats and its metabolism by rat liver microsomes. Dolan, ME; Gupta, E; Roy, SK, 1995)	0.29
" The median elimination half-life (t1/2) in patients receiving concomitant valproate (VPA) was 43."	( Pharmacokinetic interactions between lamotrigine and other antiepileptic drugs in children with intractable epilepsy. Boreus, L; Eriksson, AS; Hoppu, K; Nergårdh, A, 1996)	0.29
" Estimation of the pharmacokinetic parameters in each drug was performed by Higuchi's Bayesian program, PEDA Pearson's correlation coefficient (r) between clearance and body weight was calculated for each drug."	( Clearance of phenytoin and valproic acid is affected by a small body weight reduction in an epileptic obese patient: a case study. Ashikari, Y; Chiba, S; Kodama, Y; Kuranari, M; Sakata, T; Takeyama, M, 1996)	0.29
" Routine clinical pharmacokinetic data (N = 1,010) collected from 466 patients receiving carbamazepine were analyzed according to a simple steady-state pharmacokinetic model with the use of NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data."	( Detection of carbamazepine drug interaction by multiple peak approach screening using routine clinical pharmacokinetic data. Aoyama, T; Yukawa, E, 1996)	0.29
" The results showed that both mean Cmax and AUC of DTZ were lower (871."	( Effect of phenobarbital pretreatment on the pharmacokinetics and metabolism of diltiazem in rats. Buckley, SJ; Cameron, R; Feng, JD; Jordan, J; Yeung, PK, 1996)	0.7
" This study compares the pharmacokinetics of CBZ-CO against CBZ-CR in patients with epilepsies chronically treated with CBZ in monotherapy or CBZ-PB in bitherapy, the effect of PB on CBZ-CO and CBZ-CR pharmacokinetic parameters, and the effect of the two formulations of CBZ on PB pharmacokinetic parameters."	( Steady state pharmacokinetics of carbamazepine-phenobarbital interaction in patients with epilepsy. Barra, Y; Bonneton, J; Genton, P; Iliadis, A; Mesdjian, E; Sennoune, S, 1996)	0.55
" Plasma concentrations of idebenone and its main metabolites were determined and the pharmacokinetic parameters of idebenone after single and repeated doses were estimated."	( Plasma concentrations and pharmacokinetics of idebenone and its metabolites following single and repeated doses in young patients with mitochondrial encephalomyopathy. Autret, E; Blin, O; Desnuelle, C; Durand, A; Joubert, M; Legout, V; Pinsard, N; Pisano, P; Serratrice, G, 1996)	0.29
" Thiamine diphosphate administered intraperitoneally in a dose of 10 mg/kg (one time a day for a week) does not change pharmacokinetic and analgesic effect of naproxene."	( [The modification of the pharmacokinetics and analgesic effect of naproxen by cimetidine, phenobarbital and thiamine diphosphate]. Pentiuk, AA; Stanislavchuk, NA; Vovk, OG, )	0.35
" IFO pharmacokinetic studies were performed on the first and third day of each course."	( Phenobarbital administration does not affect high-dose ifosfamide pharmacokinetics in humans. Lokiec, F; Santoni, J; Tubiana-Hulin, M; Weill, S, 1996)	1.74
" There were no differences in pharmacokinetic parameters for lidocaine between the UT and PB groups."	( Effect of phenobarbital on the pharmacokinetics of lidocaine, monoethylglycinexylidide and 3-hydroxylidocaine in the rat: correlation with P450 isoform levels. Fujimori, M; Funae, Y; Imaoka, S; Nakamoto, T; Oda, Y, 1997)	0.7
"The effects of pretreatment with the enzyme inducers phenobarbital (PB) and 3-methylcholanthrene (3-MC) and the enzyme inhibitor chloramphenicol (CM) on the pharmacokinetic and pharmacodynamic parameters of azosemide were examined after intravenous (i."	( Effect of phenobarbital, 3-methylcholanthrene, and chloramphenicol pretreatment on the pharmacokinetics and pharmacodynamics of azosemide in rats. Lee, MG; Lee, SH, 1997)	0.95
"To conduct a population pharmacokinetic analysis of carbamazepine (CBZ)."	( Population pharmacokinetics of carbamazepine in adults with epilepsy. Ahman, P; Brundage, RC; Cascino, G; Graves, NM; Krause, S; Leppik, IE; Rarick, J; So, E; Wen, Y, )	0.13
"Physiologically based pharmacokinetic modeling of the parent chemical primidone and its two metabolites phenobarbital and phenylethylmalonamide (PEMA) was applied to investigate the differences of primidone metabolism among humans, rats, and mice."	( Physiologically based pharmacokinetics model of primidone and its metabolites phenobarbital and phenylethylmalonamide in humans, rats, and mice. El-Masri, HA; Portier, CJ, 1998)	0.74
" The present pharmacokinetic study investigates the potential for modulation of these alternative pathways of IF metabolism in vivo using the adult male Fischer 344 rat model."	( Modulation of P450-dependent ifosfamide pharmacokinetics: a better understanding of drug activation in vivo. Brain, EG; Drewes, P; Gustafsson, K; Waxman, DJ; Yu, LJ, 1998)	0.3
" The in vivo modulation of these alternative, competing pathways of P-450 metabolism was investigated in pharmacokinetic studies carried out in the rat model."	( In vivo modulation of alternative pathways of P-450-catalyzed cyclophosphamide metabolism: impact on pharmacokinetics and antitumor activity. Brain, EG; Drewes, P; Gustafsson, K; Hecht, JE; Waxman, DJ; Yu, LJ, 1999)	0.3
"Plasma concentrations of lamotrigine, an antiepileptic drug obtained in three adult controlled clinical trials conducted in the United States were pooled and analyzed using NONMEM, a population pharmacokinetic computer program, to facilitate development of dosing guidelines."	( Population pharmacokinetics of lamotrigine adjunctive therapy in adults with epilepsy. Chen, C; Cox, E; Fiedler-Kelly, J; Grasela, TH; Risner, ME; Womble, GP, 1999)	0.3
" A maintenance dose of 5 mg/kg/d provided a peak concentration of 19."	( Phenobarbital dosing and pharmacokinetics in a neonate receiving extracorporeal membrane oxygenation. Buck, ML; Elliott, ES, 1999)	1.75
" Pharmacokinetic analysis revealed a volume of distribution slightly larger than expected in neonates and an elimination half-life similar to published values."	( Phenobarbital dosing and pharmacokinetics in a neonate receiving extracorporeal membrane oxygenation. Buck, ML; Elliott, ES, 1999)	1.75
" The pretreatment resulted in an increase in biological half-life (5."	( Inhibition of aldo-keto reductases by phenobarbital alters metabolism, pharmacokinetics and toxicity of doxorubicin in rats. Behnia, K; Boroujerdi, M, 1999)	0.57
" This was also the case for phenylethylmalonamide and phenobarbital but peak concentration occurred later."	( Blood and cerebrospinal fluid pharmacokinetics of primidone and its primary pharmacologically active metabolites, phenobarbital and phenylethylmalonamide in the rat. Nagaki, S; Patsalos, PN; Ratnaraj, N, )	0.59
" All data were analyzed using NONMEM to estimate pharmacokinetic parameters of PB with respect to the CYP2C19 genotype."	( CYP2C19 polymorphism effect on phenobarbitone. Pharmacokinetics in Japanese patients with epilepsy: analysis by population pharmacokinetics. Hadama, A; Higuchi, S; Ieiri, I; Mamiya, K; Ninomiya, H; Otsubo, K; Tashiro, N; Yukawa, E, )	0.13
" Pharmacokinetic interactions between antiepileptic drugs represent a major complication of epilepsy treatment with polytherapy."	( Investigation of phenobarbital-carbamazepine-valproic acid interactions using population pharmacokinetic analysis for optimisation of antiepileptic drug therapy: an overview. Yukawa, E, 2000)	0.65
" Pharmacokinetic studies involved administering phenobarbital (15 mg/kg [6."	( Effects of diet on pharmacokinetics of phenobarbital in healthy dogs. Fettman, MJ; Greco, DS; Maguire, PJ; Ogilvie, GK; Smith, MO; Turner, AS; Walton, JA, 2000)	0.83
"Volume of distribution, mean residence time, and half-life (t1/2) of phenobarbital significantly decreased, whereas clearance rate and elimination rate significantly increased with time in all groups."	( Effects of diet on pharmacokinetics of phenobarbital in healthy dogs. Fettman, MJ; Greco, DS; Maguire, PJ; Ogilvie, GK; Smith, MO; Turner, AS; Walton, JA, 2000)	0.81
"Demographic and clinical pharmacokinetic data collected from term and preterm neonates who were treated with intravenous phenobarbital have been analysed to evaluate the role of patient characteristics in pharmacokinetic parameters."	( Clinical pharmacokinetics of phenobarbital in neonates. Cranendonk, A; Graafland, O; Touw, DJ; van Weissenbruch, MM; Vermeulen, RJ, 2000)	0.81
" However, the pharmacokinetic parameters of parathion were not significantly different after pretreatment with other enzyme inducers compared with respective control rats."	( Effects of enzyme inducers or inhibitors on the pharmacokinetics of intravenous parathion in rats. Hurh, E; Kim, S; Kim, Y; Lee, A; Lee, E; Lee, M, 2000)	0.31
"To determine whether there is a pharmacokinetic interaction between the antiepileptic drugs remacemide and phenobarbitone."	( Evaluation of a pharmacokinetic interaction between remacemide hydrochloride and phenobarbitone in healthy males. Blakey, GE; Eadie, MJ; Hooper, WD; Lockton, JA; Manun'Ebo, M, 2001)	0.31
"Apparent remacemide clearance (CL/F) and elimination half-life values were unchanged after 7 days intake of the drug in the absence of phenobarbitone (1."	( Evaluation of a pharmacokinetic interaction between remacemide hydrochloride and phenobarbitone in healthy males. Blakey, GE; Eadie, MJ; Hooper, WD; Lockton, JA; Manun'Ebo, M, 2001)	0.31
" To avoid complex pharmacokinetic interactions among multiple antiepileptic drugs, the data on serum concentrations in the current study were collected from patients who were co-administered only one additional antiepileptic drug (phenobarbital-carbamazepine, phenobarbital-valproic acid, or carbamazepine-valproic acid) or who received monotherapy."	( Pharmacokinetic interactions among phenobarbital, carbamazepine, and valproic acid in pediatric Japanese patients: clinical considerations on steady-state serum concentration-dose ratios. Aoyama, T; Higuchi, S; Hokazono, T; Ohdo, S; Satou, M; Yukawa, E, 2000)	0.77
" The results also revealed statistically significant greater total body clearance for phenobarbital and consequently a shorter half-life with MDAC treatment versus either urinary alkalinization alone or the combined use of both."	( Pharmacokinetics of phenobarbital during certain enhanced elimination modalities to evaluate their clinical efficacy in management of drug overdose. Abdel-Rahman, HM; Mohammed Ebid, AH, 2001)	0.86
" Pharmacokinetic parameters were calculated and compared in the two groups."	( Effect of smoking on single dose pharmacokinetics of phenobarbital. Farsam, H; Jahanzad, F; Mahmoudian, M; Mirfazaelian, A; Tabatabaei-far, M, 2001)	0.56
" The pharmacokinetic parameters were analyzed by analysis of variance followed by the Tukey-Kramer test."	( Pharmacokinetic interaction between albendazole sulfoxide enantiomers and antiepileptic drugs in patients with neurocysticercosis. Dreossi, SA; Garcia, FS; Lanchote, VL; Takayanagui, OM, 2002)	0.31
"To evaluate potential pharmacokinetic interactions between phenobarbitone and retigabine, a new antiepileptic drug."	( Lack of pharmacokinetic interaction between retigabine and phenobarbitone at steady-state in healthy subjects. Ferron, GM; Parks, V; Patat, A; Rolan, P; Troy, SM, 2003)	0.32
"There was no pharmacokinetic interaction between retigabine and phenobarbitone in healthy subjects."	( Lack of pharmacokinetic interaction between retigabine and phenobarbitone at steady-state in healthy subjects. Ferron, GM; Parks, V; Patat, A; Rolan, P; Troy, SM, 2003)	0.32
" Mean (95% confidence interval or median and range for Cmax) pharmacokinetic parameters were: area under curve [AUC (0, infinity)]: 4259 (3169, 5448) mg l(-1)."	( Pharmacokinetics and clinical effect of phenobarbital in children with severe falciparum malaria and convulsions. Kokwaro, GO; Muchohi, SN; Newton, CR; Ogutu, BR; Otieno, GO, 2003)	0.59
"To develop a population pharmacokinetic model to evaluate the effects of variety of covariates on clearance of carbamazepine (CBZ) and its main metabolite carbamazepine-10,11-epoxide (CBZE) in Chinese population."	( Population pharmacokinetic modeling of steady state clearance of carbamazepine and its epoxide metabolite from sparse routine clinical data. Jiao, Z; Shi, XJ; Zhao, ZG; Zhong, MK, 2004)	0.32
" Age was identified as a statistically significant predictor of CL/F at multiple regression analysis, but it accounted for only a modest component of the interindividual pharmacokinetic variation."	( Phenobarbital pharmacokinetics in old age: a case-matched evaluation based on therapeutic drug monitoring data. Battino, D; Croci, D; Mamoli, D; Messina, S; Perucca, E; Ratti, S, 2005)	1.77
" A one-compartment open pharmacokinetic model with first-order elimination was used."	( Population pharmacokinetic investigation of phenobarbital by mixed effect modelling using routine clinical pharmacokinetic data in Japanese neonates and infants. Minemoto, M; Suematsu, F; Yukawa, E; Yukawa, M, 2005)	0.59
" The method has been successfully used to study the pharmacokinetics of levodopa in vivo; the values of the pharmacokinetics parameters Cmax, AUC(0-t) and Tmax were 16."	( Microdialysis sampling and high-performance liquid chromatography with chemiluminescence detection for in-vivo on-line determination and study of the pharmacokinetics of levodopa in blood. Deyong, H; Funan, C; Yingxue, Z; Zhujun, Z, 2005)	0.33
" Any pharmacokinetic contribution was ascertained by measurement of brain antiepileptic drug (AED) concentrations."	( Pharmacodynamic and/or pharmacokinetic characteristics of interactions between loreclezole and four conventional antiepileptic drugs in pentylenetetrazole-induced seizures in mice: an isobolographic analysis. Czuczwar, SJ; Luszczki, JJ; Patsalos, PN; Ratnaraj, N, 2005)	0.33
"To characterize the magnitude, time course, and specificity of phenobarbital (PB)-mediated enzyme induction, and further, to develop an integrated pharmacokinetic (PK)-enzyme model describing the changes in the activities of CYP enzymes as well as in the PK of PB."	( A mechanism-based integrated pharmacokinetic enzyme model describing the time course and magnitude of phenobarbital-mediated enzyme induction in the rat. Karlsson, MO; Magnusson, MO; Sandström, R, 2006)	0.79
" The half-life of the induction process was estimated to be 2 days for CYP1A2, CYP3A1/2, and CYP2B1/2, and 3 days for androstenedione producing enzymes."	( A mechanism-based integrated pharmacokinetic enzyme model describing the time course and magnitude of phenobarbital-mediated enzyme induction in the rat. Karlsson, MO; Magnusson, MO; Sandström, R, 2006)	0.55
"These findings indicated that the genetic polymorphisms of CYP2C19 contribute to the pharmacokinetic variability of phenytoin and phenobarbital, the poor metabolizers of CYP2C19, which are relatively common in Asian groups."	( Effect of CYP2C19 genetic polymorphism on pharmacokinetics of phenytoin and phenobarbital in Japanese epileptic patients using Non-linear Mixed Effects Model approach. Mamiya, K; Yukawa, E, 2006)	0.77
" Brain AED concentrations were also measured so as to ascertain any pharmacokinetic contribution to the pharmacodynamic interactions."	( Characterization of the anticonvulsant, behavioral and pharmacokinetic interaction profiles of stiripentol in combination with clonazepam, ethosuximide, phenobarbital, and valproate using isobolographic analysis. Czuczwar, SJ; Luszczki, JJ; Patsalos, PN; Ratnaraj, N, 2006)	0.53
" However, these interactions were complicated by changes in brain AED concentrations consequent to pharmacokinetic interactions."	( Characterization of the anticonvulsant, behavioral and pharmacokinetic interaction profiles of stiripentol in combination with clonazepam, ethosuximide, phenobarbital, and valproate using isobolographic analysis. Czuczwar, SJ; Luszczki, JJ; Patsalos, PN; Ratnaraj, N, 2006)	0.53
" However, these conclusions are confounded by the fact that STP is associated with significant pharmacokinetic interactions."	( Characterization of the anticonvulsant, behavioral and pharmacokinetic interaction profiles of stiripentol in combination with clonazepam, ethosuximide, phenobarbital, and valproate using isobolographic analysis. Czuczwar, SJ; Luszczki, JJ; Patsalos, PN; Ratnaraj, N, 2006)	0.53
" The pharmacokinetics of the 260 PB concentrations at a steady-state obtained from 79 patients was described with a one-compartment open pharmacokinetic model with first-order elimination."	( Population estimation of the effects of cytochrome P450 2C9 and 2C19 polymorphisms on phenobarbital clearance in Japanese. Goto, S; Ishitsu, T; Murata, T; Nakada, N; Nakagawa, K; Seo, T; Ueda, N, 2007)	0.56
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."	( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds. Lombardo, F; Obach, RS; Waters, NJ, 2008)	0.35
" The elimination half-life of serum phenobarbital in dogs with urine alkalinization was shortened and Cl(R) increased when compared with dogs with urine acidification."	( Effects of urine pH modification on pharmacokinetics of phenobarbital in healthy dogs. Fujiwara, M; Fukunaga, K; Mishima, K; Muto, M; Orito, K; Saito, M, 2008)	0.87
" Enzyme kinetic parameters (K(m) and V(max)) and pharmacokinetic properties of three probe drugs were compared using wild-type and humanized UGT1 mice that express the Gilbert's UGT1A1*28 allele [Tg(UGT1(A1*28)) Ugt1(-/-) mice]."	( A humanized UGT1 mouse model expressing the UGT1A1*28 allele for assessing drug clearance by UGT1A1-dependent glucuronidation. Cai, H; Chen, S; Hotz, K; La Placa, DB; Nguyen, N; Peterkin, V; Stevens, JC; Tukey, RH; Yang, YS, 2010)	0.36
"The aim of the present study was to build population pharmacokinetic models for the clearance of valproate (VPA) in 2 separate populations of Serbian patients with epilepsy, children and adults."	( Factors influencing valproate pharmacokinetics in children and adults. Jankovic, S; Jankovic, SM; Milovanovic, JR, 2010)	0.36
" The pharmacokinetic models obtained were validated in groups of 15 epileptic patients, each showing good predictive performance of the model."	( Factors influencing valproate pharmacokinetics in children and adults. Jankovic, S; Jankovic, SM; Milovanovic, JR, 2010)	0.36
" Compared with values determined when LEV was administered alone, concurrent administration of PB resulted in a decrease in LEV peak concentration (C(max) ) from 32."	( The pharmacokinetics of levetiracetam in healthy dogs concurrently receiving phenobarbital. Moore, SA; Muñana, KR; Nettifee-Osborne, JA; Papich, MG, 2011)	0.6
" Pharmacokinetic parameters were then calculated."	( Phenobarbital for neonatal seizures in hypoxic ischemic encephalopathy: a pharmacokinetic study during whole body hypothermia. Cavallaro, G; Donzelli, G; Favelli, F; Filippi, L; Fiorini, P; Guerrini, R; la Marca, G; Malvagia, S, 2011)	1.81
"The aim of the present study was to build population pharmacokinetic models for the clearance of carbamazepine (CBZ) in two separate populations of Serbian patients with epilepsy, children and adults."	( Factors influencing carbamazepine pharmacokinetics in children and adults: population pharmacokinetic analysis. Jankovic, SM; Milovanovic, JR, 2011)	0.37
" The pharmacokinetic models obtained were validated in groups of 18 children and 13 adults with epilepsy."	( Factors influencing carbamazepine pharmacokinetics in children and adults: population pharmacokinetic analysis. Jankovic, SM; Milovanovic, JR, 2011)	0.37
" However, because of sampling restrictions, it is often difficult to perform traditional pharmacokinetic studies in neonates and infants."	( Population pharmacokinetics of phenobarbital by mixed effect modelling using routine clinical pharmacokinetic data in Japanese neonates and infants: an update. Aki, H; Ikeda, H; Mimemoto, M; Suematsu, F; Takiguchi, T; Yukawa, E; Yukawa, M, 2011)	0.66
" A one-compartment pharmacokinetic model with first-order elimination was used."	( Population pharmacokinetics of phenobarbital by mixed effect modelling using routine clinical pharmacokinetic data in Japanese neonates and infants: an update. Aki, H; Ikeda, H; Mimemoto, M; Suematsu, F; Takiguchi, T; Yukawa, E; Yukawa, M, 2011)	0.66
"The final pharmacokinetic parameters were CL/F (mL/h) = (5."	( Population pharmacokinetics of phenobarbital by mixed effect modelling using routine clinical pharmacokinetic data in Japanese neonates and infants: an update. Aki, H; Ikeda, H; Mimemoto, M; Suematsu, F; Takiguchi, T; Yukawa, E; Yukawa, M, 2011)	0.66
" A population pharmacokinetic model was developed using NONMEM."	( Drug interaction and pharmacokinetic modeling of oxcarbazepine in korean patients with epilepsy. Hong, SB; Huh, W; Joo, EY; Kim, JR; Kim, SR; Ko, JW; Lee, SY; Park, KJ; Seo, DW, )	0.13
" In population pharmacokinetic modeling, the apparent clearance of OHC was higher by 31."	( Drug interaction and pharmacokinetic modeling of oxcarbazepine in korean patients with epilepsy. Hong, SB; Huh, W; Joo, EY; Kim, JR; Kim, SR; Ko, JW; Lee, SY; Park, KJ; Seo, DW, )	0.13
" Population pharmacokinetic analysis showed that the apparent clearance of OHC increased with comedication with EIAEDs."	( Drug interaction and pharmacokinetic modeling of oxcarbazepine in korean patients with epilepsy. Hong, SB; Huh, W; Joo, EY; Kim, JR; Kim, SR; Ko, JW; Lee, SY; Park, KJ; Seo, DW, )	0.13
"A pharmacokinetic model was developed for PG co-administered with paracetamol or phenobarbital in neonates."	( Developmental pharmacokinetics of propylene glycol in preterm and term neonates. Allegaert, K; Danhof, M; De Cock, RF; de Hoon, J; Knibbe, CA; Kulo, A; Verbesselt, R, 2013)	0.62
" The clearance of phenobarbital was linearly related to body weight and matured with increasing age with a maturation half-life of 22."	( Population pharmacokinetics of phenobarbital in infants with neonatal encephalopathy treated with therapeutic hypothermia. Barks, JD; Bhatt-Mehta, V; Dillon, CH; Ng, CM; Shellhaas, RA, 2013)	1.01
" The objective of this study is to characterize the absolute bioavailability of phenobarbital in neonates and young infants, a pharmacokinetic parameter which has not yet been investigated."	( Pharmacokinetics and absolute bioavailability of phenobarbital in neonates and young infants, a population pharmacokinetic modelling approach. Boulamery, A; Brevaut-Malaty, V; Bruguerolle, B; Marsot, A; Simon, N; Vialet, R, 2014)	0.88
" Elimination half-life was about 50 h (50."	( Is switching from brand name to generic formulations of phenobarbital associated with loss of antiepileptic efficacy?: a pharmacokinetic study with two oral formulations (Luminal(®) vet, Phenoleptil(®)) in dogs. Bankstahl, JP; Bankstahl, M; Löscher, W, 2013)	0.64
"Overall, the two formulations did not differ significantly with respect to pharmacokinetic parameters when mean group parameters were compared."	( Is switching from brand name to generic formulations of phenobarbital associated with loss of antiepileptic efficacy?: a pharmacokinetic study with two oral formulations (Luminal(®) vet, Phenoleptil(®)) in dogs. Bankstahl, JP; Bankstahl, M; Löscher, W, 2013)	0.64
"To determine the effects of CYP3A5 polymorphisms on carbamazepine (CBZ) pharmacokinetic parameters when CBZ is used either as monotherapy or co-administered with phenytoin (PHT), phenobarbital (PB) or valproic acid (VPA)."	( Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients. Panomvana, D; Towanabut, S; Traiyawong, T, 2013)	0.79
" Pharmacokinetic parameters of CBZ; clearance and dose-adjusted CBZ levels in patients with different genotypes were calculated and compared."	( Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients. Panomvana, D; Towanabut, S; Traiyawong, T, 2013)	0.6
" Pharmacokinetic parameters of nicorandil and its isomers, as well as the plasma concentrations of the corresponding denitrated metabolites and also nicotinamide and nitrite were determined."	( Synthesis, antinociceptive activity and pharmacokinetic profiles of nicorandil and its isomers. Almeida, MO; Araujo, DP; César, IC; Coelho, MM; de Fátima, A; Dutra, MM; Godin, AM; Machado, RR; Menezes, RR; Oliveira, FC; Pianetti, GA; Santos, DA; Santos, JR, 2014)	0.4
"The present study aimed to establish population pharmacokinetic model for phenobarbital (PB), examining and quantifying the magnitude of PB interactions with other antiepileptic drugs concomitantly used and to demonstrate its use for individualization of PB dosing regimen in adult epileptic patients."	( Nonlinear mixed effects modelling approach in investigating phenobarbital pharmacokinetic interactions in epileptic patients. Golubović, B; Jovanović, M; Kovačević, SV; Martinović, Ž; Miljković, B; Prostran, M; Vučićević, K, 2015)	0.89
"Prospective pharmacokinetic study."	( Effect of chronic administration of phenobarbital, or bromide, on pharmacokinetics of levetiracetam in dogs with epilepsy. Muñana, KR; Nettifee-Osborne, JA; Papich, MG, )	0.41
"Compared to the PB and PB-BR groups, the BR group had significantly higher peak concentration (Cmax ) (73."	( Effect of chronic administration of phenobarbital, or bromide, on pharmacokinetics of levetiracetam in dogs with epilepsy. Muñana, KR; Nettifee-Osborne, JA; Papich, MG, )	0.41
"The population pharmacokinetic model reported here was developed using data from 2 phase 2 trials of irinotecan for treatment of malignant glioma to quantify the impact of concomitant therapy with enzyme-inducing antiepileptic drugs (EIAEDs) on irinotecan pharmacokinetics."	( Quantification of the impact of enzyme-inducing antiepileptic drugs on irinotecan pharmacokinetics and SN-38 exposure. Ames, MM; Berg, AK; Buckner, JC; Galanis, E; Jaeckle, KA; Reid, JM, 2015)	0.42
" Phenobarbital pharmacokinetic parameters (standardized intravenous loading dose was 10-20 mg/kg, maintenance dose 2-6 mg/kg/day) were computed using non-compartmental analysis."	( Effect of co-medication on the pharmacokinetic parameters of phenobarbital in asphyxiated newborns. Hronová, K; Pokorná, P; Šíma, M; Slanař, O, 2015)	1.57
"The aims of the study were to develop a population pharmacokinetic model of orally administered brivaracetam in paediatric patients and to provide dosing suggestions."	( Brivaracetam population pharmacokinetics in children with epilepsy aged 1 month to 16 years. Schoemaker, R; Stockis, A; Wade, JR, 2017)	0.46
" Pharmacokinetic analysis was performed using non-linear mixed effects modelling, and a stepwise covariate search was used to determine factors influencing brivaracetam clearance."	( Brivaracetam population pharmacokinetics in children with epilepsy aged 1 month to 16 years. Schoemaker, R; Stockis, A; Wade, JR, 2017)	0.46
"An external evaluation of phenobarbital population pharmacokinetic model described by Marsot et al."	( Phenobarbital in intensive care unit pediatric population: predictive performances of population pharmacokinetic model. Blin, O; Chasseloup, E; Guilhaumou, R; Marsot, A; Michel, F; Paut, O, 2017)	2.2
"In covariate (sub)models of population pharmacokinetic models, most covariates are normalized to the median value; however, for body weight, normalization to 70 kg or 1 kg is often applied."	( The Influence of Normalization Weight in Population Pharmacokinetic Covariate Models. Aarons, L; Calvier, EAM; Goulooze, SC; Knibbe, CAJ; Krekels, EHJ; Välitalo, PAJ; Völler, S, 2019)	0.51
" Individual PK parameters - volume of distribution (Vd) and clearance (CL) were calculated in a one-compartmental pharmacokinetic model."	( Phenobarbital pharmacokinetics in neonates and infants during extracorporeal membrane oxygenation. Pokorná, P; Šíma, M; Slanař, O; Tibboel, D; Vobruba, V, 2018)	1.92
" Median optimal phenobarbital loading dose (LD) and maintenance dose (MD), calculated from pharmacokinetic data, were 15 mg/kg and 4 mg/kg/day, respectively."	( Phenobarbital pharmacokinetics in neonates and infants during extracorporeal membrane oxygenation. Pokorná, P; Šíma, M; Slanař, O; Tibboel, D; Vobruba, V, 2018)	2.27
" Pharmacokinetic data for this patient population is lacking and would assist in dosing decisions."	( Phenobarbital population pharmacokinetics across the pediatric age spectrum. Galati, M; Kayyal, SY; Moffett, BS; Placencia, JL; Riviello, JJ; Rodman, EA; Weingarten, MM, 2018)	1.92
"A retrospective population pharmacokinetic analysis was designed for all pediatric patients <19 years of age initiated on phenobarbital at our institution from January 2011 to June 2017."	( Phenobarbital population pharmacokinetics across the pediatric age spectrum. Galati, M; Kayyal, SY; Moffett, BS; Placencia, JL; Riviello, JJ; Rodman, EA; Weingarten, MM, 2018)	2.13
" A population pharmacokinetic approach and nonlinear mixed effects modeling were used to analyze the data."	( Population pharmacokinetics of extended-release levetiracetam in epileptic dogs when administered alone, with phenobarbital or zonisamide. Muñana, KR; Nettifee, JA; Otamendi, AJ; Papich, MG, 2018)	0.69
" Pharmacokinetic analyses were performed using non-linear mixed effects modelling; clinical effectiveness was defined as no use of additional anti-epileptic drugs."	( Phenobarbital, Midazolam Pharmacokinetics, Effectiveness, and Drug-Drug Interaction in Asphyxiated Neonates Undergoing Therapeutic Hypothermia. Cools, F; de Haan, TR; Dijk, PH; Dijkman, KP; Egberts, TCG; Favié, LMA; Groenendaal, F; Huitema, ADR; Nuytemans, DHGM; Rademaker, CMA; Rijken, M; Simons, SHP; van Bel, F; van den Broek, MPH; van der Lee, JH; van Heijst, A; van Straaten, HLM; Zecic, A; Zonnenberg, IA, 2019)	1.96
"To develop a population pharmacokinetic model for IV phenobarbital in neonates following cardiac surgery and perform simulations to identify optimal dosing regimens."	( Population Pharmacokinetics of IV Phenobarbital in Neonates After Congenital Heart Surgery. Abend, NS; Massey, SL; Naim, MY; Thibault, C; Zuppa, AF, 2020)	1.09
"Retrospective single-center pharmacokinetic study."	( Population Pharmacokinetics of IV Phenobarbital in Neonates After Congenital Heart Surgery. Abend, NS; Massey, SL; Naim, MY; Thibault, C; Zuppa, AF, 2020)	0.84
"A population pharmacokinetic model was developed using nonlinear mixed-effects modeling."	( Population Pharmacokinetics of IV Phenobarbital in Neonates After Congenital Heart Surgery. Abend, NS; Massey, SL; Naim, MY; Thibault, C; Zuppa, AF, 2020)	0.84
"Retrospective pilot population pharmacokinetic analysis."	( Rapid Increase in Clearance of Phenobarbital in Neonates on Extracorporeal Membrane Oxygenation: A Pilot Retrospective Population Pharmacokinetic Analysis. Knibbe, CAJ; Krekels, EHJ; Michaličková, D; Pokorná, P; Slanař, O; Tibboel, D, 2020)	0.84
" To date, several population pharmacokinetic models have been developed for phenobarbital, these showing a number of significant predictors of phenobarbital clearance and volume of distribution."	( Pharmacokinetic variability of phenobarbital: a systematic review of population pharmacokinetic analysis. Leelakanok, N; Methaneethorn, J, 2021)	1.14
"Phenobarbital clearance may be predicted from previously developed population pharmacokinetic models and their significant covariate-parameter relationships along with Bayesian forecasting."	( Pharmacokinetic variability of phenobarbital: a systematic review of population pharmacokinetic analysis. Leelakanok, N; Methaneethorn, J, 2021)	2.35
"Several studies have reported population pharmacokinetic models for phenobarbital (PB), but the predictive performance of these models has not been well documented."	( External evaluation of the predictive performance of seven population pharmacokinetic models for phenobarbital in neonates. Chae, JW; Jiao, Z; Jung, WJ; Ryu, S; Yun, HY, 2021)	1.07
" A literature review was conducted through PubMed to identify population pharmacokinetic models."	( External evaluation of the predictive performance of seven population pharmacokinetic models for phenobarbital in neonates. Chae, JW; Jiao, Z; Jung, WJ; Ryu, S; Yun, HY, 2021)	0.84
" Seven population pharmacokinetic studies of PB were identified as relevant in the literature search and included for our evaluation."	( External evaluation of the predictive performance of seven population pharmacokinetic models for phenobarbital in neonates. Chae, JW; Jiao, Z; Jung, WJ; Ryu, S; Yun, HY, 2021)	0.84
" The whole-body physiologically based pharmacokinetic (PBPK) models for quinine, phenobarbital, and quinine-phenobarbital coadministration were constructed based on the previously published information using Simbiology®."	( Physiologically based pharmacokinetic modeling for dose optimization of quinine-phenobarbital coadministration in patients with cerebral malaria. Karbwang, J; Na-Bangchang, K; Rajoli, RKR; Sae-Heng, T; Siccardi, M, 2022)	1.17

Compound-Compound Interactions

High-dose topiramate combined with high-dose lidocaine infusion may be an effective treatment option for children with AERRPS. Study evaluated lamotrigine alone or in combination with phenobarbital and phenytoin.

Excerpt	Reference	Relevance
"The effect of age on the steady state levels of phenobarbitone, alone and when given with phenytoin, sodium valproate and ethosuccimide has been measured in 1 361 children whose ages ranged from one month to 12 years."	( [Plasma levels of phenobarbital in epileptic children. Effect of combination with other anticonvulsants]. Antonozzi, I; Benedetti, P; Curatolo, P; Porro, G, )	0.47
"14C-Isoniazid (20 mg/kg po or iv) was administered alone or in combination with aspirin (100 mg/kg po), rifampin (30 mg/kg po), ethambutol (100 mg/kg po), or ethanol (3 g/kg po) to rats."	( Drug interactions with isoniazid metabolism in rats. Solomonraj, G; Thomas, BH, 1977)	0.26
" Administration of nicotinamide in combination with ziksorin or phenobarbital enhanced the enzyme-inducing effects of the latter."	( [Effect of nicotinic acid, nicotinamide and its combination with ziksorin and phenobarbital on the UDP glucuronyl transferase activity of the hepatic endoplasmic reticulum in the rat]. Bushma, MI; Legon'kova, LF; Lukienko, PI, )	0.6
"5, and 15 mg/kg), and valproic acid (40, 60, 80, and 120 mg/kg), and those of phenobarbital (10 and 20 mg/kg) in combination with phenytoin (2."	( Effects of phenobarbital in combination with phenytoin or valproic acid on the delayed-matching-to-sample performance of pigeons. Karas, CA; Picker, M; Poling, A, 1986)	0.89
"025% 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) for two weeks combined with partial hepatectomy at the end of the first week and followed by long-term treatment with phenobarbital (PB) or 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) from week 3 to week 86 resulted in dose-dependent development of liver and thyroid neoplastic and preneoplastic lesions."	( Dose-dependent induction of liver and thyroid neoplastic lesions by short-term administration of 2-amino-3-methylimidazo[4,5-f]quinoline combined with partial hepatectomy followed by phenobarbital or low dose 3'-methyl-4-dimethylaminoazobenzene promotion. Asamoto, M; Inoue, T; Ito, N; Nagao, M; Ogiso, T; Tsuda, H, 1988)	0.66
" Purely additive interactions were found for the anticonvulsant effect when valproate was combined with carbamazepine as well as with phenobarbital."	( Anticonvulsant potency and neurotoxicity of valproate alone and in combination with carbamazepine or phenobarbital. Bourgeois, BF, 1988)	0.69
" However, because PB had a markedly lower TI than PHT in this model, the TI of the drug combination was lower than the TI of PHT."	( Antiepileptic drug combinations and experimental background: the case of phenobarbital and phenytoin. Bourgeois, BF, 1986)	0.5
"Antiepileptic drugs interact with a variety of other drugs to affect the pharmacokinetic behavior of either drug."	( Drug interactions between antiepileptic drugs and other drugs. Kutt, H, 1985)	0.27
" Diphenyl hydantoin is often combined with barbiturates to treat epilepsy."	( [Drug interactions in the use of steroid hormones, especially oral contraceptives]. Bolt, HM, 1985)	0.27
" Phenytoin in combination with other drugs (anticonvulsives, antibiotics etc."	( [Effects of drug interaction in infancy (author's transl)]. Alterthum, K; Bauer, P; Stünkel, S; Windorfer, A, 1980)	0.26
" These results show that oxazepam glucuronyl transferase activity is increased by treatment with phenytoin alone or in combination with phenobarbitone in epileptic patients."	( Oxazepam pharmacokinetics in patients with epilepsy treated long-term with phenytoin alone or in combination with phenobarbitone. Hawksworth, GM; Khir, AS; Petrie, JC; Scott, AK; Steele, WH, 1983)	0.27
"Valproic acid undergoes drug-drug interactions with most of the commonly used anticonvulsants."	( Drug interactions with valproic acid. Koch, KM; Levy, RH, 1982)	0.26
" Based on previous studies, antipyrine given with phenobarbitone produced slightly more induction than phenobarbitone given alone."	( Enzyme-inducing drug combinations and their effects on liver microsomal enzyme activity in man. Gerber-Taras, E; Ohnhaus, EE; Park, BK, 1983)	0.27
"The following double-blind, randomised study dealt with three questions: (1) Is a multidimensional psychometric rating scale suitable for the measurement of mood before anaesthesia? (2) What are the effects of the new benzodiazepine-like drug zolpidem on preoperative mood compared with phenobarbital? (3) Is the combination with Promethazine suggestive? METHODS."	( [Multidimensional psychometric assessment of preoperative mood. Effects of zolpidem compared to phenobarbital combined with promethazine as premedication]. Hüppe, M; Nidermaier, B; Uhlig, T, 1995)	0.69
" Because of its widespread and long term use, carbamazepine is frequently prescribed in combination with other drugs, leading to the possibility of drug interactions."	( Clinically significant pharmacokinetic drug interactions with carbamazepine. An update. Perucca, E; Pisani, F; Spina, E, 1996)	0.29
" The study compared preanesthesiological treatment by zolpidem and phenobarbital in combination with promethazine in a clinical setting."	( Mood effects of zolpidem versus phenobarbital combined with promethazine in an anesthesiological setting. Hüppe, M; Nidermaier, B; Pestel, G; Uhlig, T, 1996)	0.81
" Patients received phenobarbitone as monotherapy or in combination with either of the antiepileptic drugs carbamazepine or valproic acid."	( Detection of a drug-drug interaction on population-based phenobarbitone clearance using nonlinear mixed-effects modeling. Aoyama, T; Higuchi, S; Ohdo, S; To, H; Yukawa, E, 1998)	0.3
" These findings provide a molecular explanation for the ability of disparate chemicals to induce CYP3A4 levels and, furthermore, provide a basis for developing in vitro assays to aid in predicting whether drugs will interact in humans."	( The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. Kliewer, SA; Lehmann, JM; McKee, DD; Moore, JT; Watson, MA; Willson, TM, 1998)	0.3
" When phenobarbital is used in combination with bromide, a reasonable therapeutic range for serum phenobarbital concentrations is 9 to 36 micrograms/ml, although in some dogs treated with bromide, phenobarbital can eventually be discontinued."	( Therapeutic serum drug concentrations in epileptic dogs treated with potassium bromide alone or in combination with other anticonvulsants: 122 cases (1992-1996). Carrillo, J; Schwark, WS; Trepanier, LA; Van Schoick, A, 1998)	0.78
" Hence, in the present study, its (100 and 200 mg/kg) action was tested alone and in combination with phenobarbitone (20 mg/kg) and diazepam (0."	( Effect of 7-nitroindazole alone and in combination with phenobarbitone and diazepam on picrotoxin-induced convulsions in rats. Ekambaram, P; Paul, V, 2003)	0.32
" The effect of SNP was tested alone and in combination with phenobarbitone (PB), the GABA potentiating antiepileptic drug, against picrotoxin (PCT) (5 mg/kg)-induced convulsions in rats."	( Effects of sodium nitroprusside, a nitric oxide donor, on gamma-aminobutyric acid concentration in the brain and on picrotoxin-induced convulsions in combination with phenobarbitone in rats. Ekambaram, P; Paul, V, 2005)	0.33
" Drug-drug interactions (DDIs) caused by induction of CYP3A4 can result in decreased exposure to coadministered drugs, with potential loss of efficacy."	( Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. de Morais, SM; Fahmi, OA; Liras, JL; Maurer, TS; Mills, JB; Ripp, SL; Trevena, KA, 2006)	0.33
"In this paper, a high-performance thin-layer chromatography (HPTLC) method combined with densitometry has been described."	( Quantitative analysis of phenobarbital in dosage form by thin-layer chromatography combined with densitometry. Kryska, M; Matysik, G; Skalska, A; Wójciak-Kosior, M, )	0.43
"The anticonvulsant and acute adverse (neurotoxic) effects of STP in combination with the various conventional antiepileptic drugs (AEDs), at fixed ratios of 1:3, 1:1, and 3:1, were evaluated in the PTZ and chimney tests in mice using the isobolographic analysis."	( Characterization of the anticonvulsant, behavioral and pharmacokinetic interaction profiles of stiripentol in combination with clonazepam, ethosuximide, phenobarbital, and valproate using isobolographic analysis. Czuczwar, SJ; Luszczki, JJ; Patsalos, PN; Ratnaraj, N, 2006)	0.53
" This study evaluated lamotrigine alone or in combination with phenobarbital, phenytoin, or the glutamate antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801) for a proapoptotic action in the developing rat brain."	( Effects of lamotrigine alone and in combination with MK-801, phenobarbital, or phenytoin on cell death in the neonatal rat brain. Gale, K; Katz, I; Kim, J; Kondratyev, A, 2007)	0.82
" Caution may be necessary when zonisamide is given with phenobarbital and when antiepileptic therapy is changed from phenobarbital to zonisamide."	( Pharmacokinetics of zonisamide and drug interaction with phenobarbital in dogs. Egashira, N; Fujiwara, M; Fukunaga, K; Matsuo, E; Mishima, K; Muto, M; Orito, K; Saito, M; Takikawa, S, 2008)	0.84
" Seizures in three patients were stopped after high-dose lidocaine infusion (6-8 mg/kg/h) in the acute stage and three patients were stopped after high dose phenobarbital (serum level 60-80 ug/mL) combined with high-dose oral topiramate (15-20 mg/kg/day)."	( Effect of topiramate, in combination with lidocaine, and phenobarbital, in acute encephalitis with refractory repetitive partial seizures. Hsia, SH; Lin, JJ; Lin, KL; Wang, HS; Wu, CT, 2009)	0.8
" High-dose topiramate combined with high-dose lidocaine infusion or high-dose phenobarbital in the acute stage might be an effective treatment option for children with AERRPS."	( Effect of topiramate, in combination with lidocaine, and phenobarbital, in acute encephalitis with refractory repetitive partial seizures. Hsia, SH; Lin, JJ; Lin, KL; Wang, HS; Wu, CT, 2009)	0.83
" Adverse-effect profiles of the drugs in combination were determined and brain AED concentrations were measured."	( Isobolographic characterization of the anticonvulsant interaction profiles of levetiracetam in combination with clonazepam, ethosuximide, phenobarbital and valproate in the mouse pentylenetetrazole-induced seizure model. Andres-Mach, MM; Czuczwar, SJ; Dudra-Jastrzebska, M; Luszczki, JJ; Patsalos, PN; Ratnaraj, N, 2009)	0.56
" Food and Drug Administration draft drug interaction guidance as CYP3A4 inducers for clinical drug-drug interaction (DDI) studies."	( Simulation of clinical drug-drug interactions from hepatocyte CYP3A4 induction data and its potential utility in trial designs. Hayashi, M; Shou, M; Skiles, GL; Xu, Y; Zhou, Y, 2011)	0.37
" Identification and elimination of such drug-drug interactions is necessary to assure adequate immunosuppression in renal transplant recipients."	( Clinically significant drug-drug interaction between tacrolimus and phenobarbital: the price we pay. Marfo, K; Siddiqi, N, 2010)	0.6
" To demonstrate a case of a 15 year old girl suffering from refractory epilepsy with underlying focal cortical dysplasia (FCD), whose seizure deterioration was most probably associated with drug-drug interactions between prescribed common antiepileptic drugs, namely valproic acid, phenobarbital or the prodrug primidon and carbamazepine."	( Antiepleptic drug interactions: a clinical case demonstration. Klapková, E; Komárek, V; Tesfaye, H; Tesfayeová, A, 2011)	0.55
" The cases were categorized into OXC monotherapy (n = 78), OXC in combination with EIAED (n = 73), and OXC in combination with non-EIAED (n = 103)."	( Drug interaction and pharmacokinetic modeling of oxcarbazepine in korean patients with epilepsy. Hong, SB; Huh, W; Joo, EY; Kim, JR; Kim, SR; Ko, JW; Lee, SY; Park, KJ; Seo, DW, )	0.13
"The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions."	( Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. Artursson, P; Haglund, U; Karlgren, M; Kimoto, E; Lai, Y; Norinder, U; Vildhede, A; Wisniewski, JR, 2012)	0.38
" For patients who used CBZ in combination with an enzyme-inducing antiepileptic drug (AED: PHT or PB), individuals carrying the CYP3A5*1 allele (CYP3A5 expressers) showed a trend of having higher CBZ clearance and lower dose-adjusted CBZ level as compared to individuals carrying the CYP3A5*3 allele, even though no statistical significance was recorded."	( Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients. Panomvana, D; Towanabut, S; Traiyawong, T, 2013)	0.6
"When CBZ was used in combination with enzyme-inducing AED, CYP3A5 expressers yielded a trend toward greater susceptibility to change in CBZ clearance and showed lower dose-adjusted CBZ levels compared to CYP3A5 non-expressers."	( Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients. Panomvana, D; Towanabut, S; Traiyawong, T, 2013)	0.6
"The multiple drug interactions in which CAIs are involved should be carefully considered when such drugs are used in combination with the drug classes mentioned above, as the risks of developing toxicity and serious side effects if the dosages are not adjusted are high."	( Drug interaction considerations in the therapeutic use of carbonic anhydrase inhibitors. Supuran, CT, 2016)	0.43
"Multi-drug combinations often make chemotherapy difficult owing to drug-drug interactions (DDIs)."	( Drug-drug interactions among drugs prescribed for nontuberculous mycobacterial infection and epilepsy: A case report. Hatanaka, M; Ikeda, R; Matsumoto, N; Oda, Y; Sonoda, J; Tazaki, T; Yoshikawa, N, 2019)	0.51
" The extent of this drug-drug interaction (DDI) is attenuated by food intake."	( Effects of food type on the extent of drug-drug interactions between activated charcoal and phenobarbital in rats. Akiyoshi, T; Imaoka, A; Ogata, Y; Ohtani, H, 2019)	0.73
" The drug-drug interactions, which may occur among currently available AEDs, are the principal criterion taken by physicians when prescribing the AED combination to the patients."	( Polygonogram with isobolographic synergy for three-drug combinations of phenobarbital with second-generation antiepileptic drugs in the tonic-clonic seizure model in mice. Florek-Łuszczki, M; Jankiewicz, M; Kominek, M; Kozińska, J; Plewa, Z; Podgórska, D; Żółkowska, D; Łuszczki, JJ, 2021)	0.85
"To compare drug-drug interaction (DDI) between tacrolimus and different formulations of phenobarbital in paediatrics and adults."	( Drug-drug interaction comparison between tacrolimus and phenobarbital in different formulations for paediatrics and adults. Chen, J; Liu, W; Lu, X; Wang, N; Zhang, Y; Zhao, X; Zhu, L; Zuo, M, 2021)	1.09
"To assess drug-drug interactions between cannabidiol (CBD) and phenobarbital (PB) when simultaneously administered to healthy dogs."	( Drug-drug interaction between cannabidiol and phenobarbital in healthy dogs. Bartner, LR; Cribb, AE; Doran, CE; Gustafson, DL; McGrath, S; Thomas, B, 2021)	1.12
" Hence, their metabolic stability and potential involvement in relevant drug-drug interactions (DDI) are of great clinical interest, being HepaRG cells herein used as an in vitro human model."	( Study of the metabolic stability profiles of perampanel, rufinamide and stiripentol and prediction of drug interactions using HepaRG cells as an in vitro human model. Alves, G; Falcão, A; Fortuna, A; Meirinho, S; Rodrigues, M, 2022)	0.72
"This study aims to develop and validate a rapid, simple, and efficient bioanalytical method for the simultaneous quantification of phenobarbital and barbital in human whole blood using liquid-liquid extraction combined with direct analysis in real time (DART) and high-resolution mass spectrometry (HRMS)."	( Rapid quantification of phenobarbital and barbital in human whole blood by liquid-liquid extraction combined with DART-orbitrap-HRMS. Ke, S; Lian, R; Liang, C; Liang, J; Rao, Y; Wang, R; Zhang, Y, 2023)	1.42

Bioavailability

Using an incompletely randomized crossover study design, the oral bioavailability characteristics of 7 different brands of phenobarbital tablets, USP, 100 mg was investigated in 5 adult, male volunteers. The data suggest that absolute bioavailability of phen Bars may be reduced when induration develops at the injection or infusion site in patients treated parenterally.

Excerpt	Reference	Relevance
" Possible drug interactions were detected by the occurrence of side-effects and interference with bioavailability of the new analgesic, also by changes in vital signs or in various laboratory tests."	( Nefopam HCl interaction study with eight other drugs. Back, EL; Cohen, A; Lasseter, KC, 1976)	0.26
" A kinetic model study on the transfer constants between various body compartments has indicated that rifampicin is rapidly absorbed from the intestine and that the absorption rate increases with time."	( Clinical pharmacokinetics of rifampicin. Acocella, G, )	0.13
" New knowledge of the pharmacokinetics of phenytoin has led to a better understanding of the drug's bioavailability and uses."	( Recent advances in drug therapy for epilepsy. Bruni, J, 1979)	0.26
" This new dissolution tester possibly can be useful in determining drug release from solid dosage forms and correlating it with in vivo bioavailability because dissolution rate can be controlled easily with the adjustment of air pressure without complicated changes in the apparatus, there is no excessive settling of particles, and complete drug dissolution can be achieved with no clogging of the screen."	( New in vitro dissolution test apparatus. Nasir, SM; Nasir, SS; Wilken, LO, 1979)	0.26
"Using an incompletely randomized crossover study design, the oral bioavailability characteristics of 7 different brands of phenobarbital tablets, USP, 100 mg was investigated in 5 adult, male volunteers."	( In vitro and in vivo characteristics of some commercial phenobarbital tablets. Sylvestri, MF; Ueda, CT, 1979)	0.71
" The absorption rate is faster using suppositories with a lower melting-point (32."	( [Rectal absorption of phenobarbital in children as affected by different vehicles]. Gladtke, E; Heimann, G; Neuwald, F, 1978)	0.57
"Theophylline bioavailability following chronic dosing of an elixir and two commercial tablet formulations (I and II) relative to an acute dose of elixir was evaluated in healthy volunteers."	( Theophylline bioavailability following chronic dosing of an elixir and two solid dosage forms. Azarnoff, DL; Fixley, M; Shen, DD, 1978)	0.26
" The absorption rate and fraction are very much dependent on the pharmaceutical preparation, and changes of brand may alter the plasma level of phenytoin in spite of unaltered dose."	( Clinical pharmacokinetics of anticonvulsants. Dam, M; Hvidberg, EF, 1976)	0.26
" Intramuscular phenobarbitone is well absorbed in children with severe malaria; the optimum prophylactic anticonvulsant dose remains to be determined."	( Absorption of intramuscular phenobarbitone in children with severe falciparum malaria. Chongsuphajaisiddhi, T; Holloway, P; Kuile, F; Maelankirri, L; Nosten, F; White, NJ, 1992)	0.28
" Bioavailability after the oral administration of PB-PC to rabbits with a dose of 15 mg/kg equivalent to PB was compared with that of PB crystals."	( Dissolution and bioavailability of phenobarbital in solid dispersion with phosphatidylcholine. Fujii, M; Harada, K; Kakinuma, K; Matsumoto, M, 1991)	0.56
" The complete oral bioavailability of VPD and the fact that the AUC of VPA obtained after oral administration of VPD was not higher than that obtained after the iv injection of VPD indicates that the gastrointestinal tract is not one of the metabolic sites of VPD to VPA conversion."	( The disposition of valpromide in rats and the isolated perfused rat liver. Bar-On, H; Bialer, M; Billig, H; Ziv, E, )	0.13
" However, elevation of gastric pH with sodium bicarbonate prior to oral administration of ddlno was not effective in increasing the bioavailability of the parent drug."	( Pharmacokinetics of the anti-AIDS drug 2',3'-dideoxyinosine in the rat. Badr, MZ; Mason, WD; Ray, GF, )	0.13
"Effect of chronic administration of aspirin, phenobarbitone and oxytetracycline under therapeutic doses on the bioavailability of vitamin A was determined in different groups of albino rats."	( Effect of chronic administration of aspirin, phenobarbitone and oxytetracycline on the plasma levels of vitamin A in albino rats. Hashmi, AS; Maqbool, T; Shah, BH, 1990)	0.28
" Inhibition of the formation of the reactive metabolite of paracetamol or reduction of the absorption rate of paracetamol seem to be unlikely as mechanisms underlying the ASA-induced effect."	( Reduction by acetylsalicylic acid of paracetamol-induced hepatic glutathione depletion in rats treated with 4,4'-dichlorobiphenyl, phenobarbitone and pregnenolone-16-alpha-carbonitrile. De Vries, J; Groot, EJ; van Bree, L, 1989)	0.28
") investigations as well as bioavailability studies of PB preparations."	( Pharmacokinetic equivalence of 5(ethyl(2H)5)- and unlabelled phenobarbitone. Benchekroun, Y; Brazier, JL; Cherrah, Y; Falconnet, JB; Ribon, B, 1989)	0.28
" The purpose of this study was to determine the relative bioavailability and time course of absorption of the commercially available parenteral phenobarbital sodium solution administered rectally in comparison with the same preparation given intramuscularly."	( Relative bioavailability of rectally administered phenobarbital sodium parenteral solution. Ehresman, DJ; Graves, NM; Holmes, GB; Jones-Saete, C; Kriel, RL; Ong, B, )	0.59
" The systemic bioavailability was observed to be higher in protein energy malnutrition."	( Pharmacokinetics of phenobarbitone in protein energy malnutrition. Raina, RK; Sharma, DB; Syed, GB, 1986)	0.27
" The bioavailability of antipyrine was only 20% due to first-pass metabolism."	( The effect of induction with phenobarbital on the kinetics and bioavailability of antipyrine in the dog. Abramson, FP, )	0.42
" Mean bioavailability was 88."	( Pharmacokinetics of single doses of phenobarbital given intravenously and orally to dogs. Pedersoli, WM; Ravis, WR; Wike, JS, 1987)	0.55
" Bioavailability of prednisolone after the oral administration of prednisone and methylprednisolone ranged from 86% to 104% during anticonvulsant therapy."	( Prednisolone and methylprednisolone kinetics in children receiving anticonvulsant therapy. Bartoszek, M; Brenner, AM; Szefler, SJ, 1987)	0.27
" The likely causes of this fact were: too low doses prescribed (55% of the patients were given doses below the generally recommended), lower bioavailability of PHT (27% of patients had no therapeutic level of the drug in the serum, despite doses exceeding 5 mg/kg); or drug interaction."	( [Characteristics of the clinical features and pharmacological treatment of epileptics with frequent seizures]. Buksowicz, C; Horyd, W; Koziak, M; Kuran, W; Lipczyńska-Lojkowska, W; Niedzielska, K; Witkowska-Olearska, K, )	0.13
"The bioavailability of dexamethasone (DEX) has recently been demonstrated to be a critical factor in determining Dexamethasone Suppression Test (DST) status in psychiatric patients."	( Dexamethasone bioavailability: implications for DST research. Lowy, MT; Meltzer, HY, 1987)	0.27
" The bioavailability of two drug forms-phenobarbital and phenobarbital-sodium--is almost equal after rectal and oral administration."	( Biopharmaceutical investigation of rectal suppositories. Part 2(1): Pharmaceutical and biological availability of phenobarbital and phenobarbital-sodium. Bantutova, I; Kirchev, D; Lambov, N; Minkov, E; Tencheva, J, 1985)	0.75
" The mechanisms responsible for these effects have not been elucidated and possibly include decreased bioavailability or compliance, increased metabolic clearance, or decreased plasma protein binding."	( Effects of pregnancy on antiepileptic drug utilization. Levy, RH; Yerby, MS, 1985)	0.27
" The effect of the volume of the perfusate on the absorption rate constant of phenobarbital, phenol red, tyrosine, and propranolol was studied."	( Mechanism of nasal absorption of drugs I: Physicochemical parameters influencing the rate of in situ nasal absorption of drugs in rats. Huang, CH; Hussain, A; Kimura, R; Nassar, RB, 1985)	0.5
" These mechanisms include: (1) impaired hepatic drug metabolism due to inhibition of hepatic microsomal enzymes, (2) reduced hepatic blood flow, resulting in decreased clearance of drugs that are highly extracted by the liver, (3) increased potential for myelosuppression when administered concurrently with other drugs capable of causing myelosuppression, and (4) altered bioavailability of acid-labile drugs."	( Review of cimetidine drug interactions. Darvey, DL; Sorkin, EM, 1983)	0.27
" Carbamazepine is well absorbed and largely metabolized."	( Pharmacokinetics of antiepileptic drugs. Neuvonen, PJ; Tokola, RA, 1983)	0.27
"A three-way crossover study was conducted with 24 healthy male volunteers to determine the relative bioavailability of four different 100-mg phenobarbital tablets compared with a reference elixir."	( Absorption of phenobarbital from tablets and elixir. Meyer, MC; Raghow, G; Rotenberg, KS; Schary, WL; Straughn, AB, 1984)	0.83
"It is now recognized that intestinal metabolism is one of the major factors affecting the bioavailability of orally administered, natural and synthetic estrogens."	( Drug effects on the intestinal absorption of estrogens. Dada, OA; Martins, OO, 1983)	0.27
" Absolute bioavailability of IM PB was 101 +/- 11%."	( Kinetics of phenobarbital in normal subjects and epileptic patients. Comfort, CP; Friel, PN; Kaluzny, SP; Levy, RH; Wilensky, AJ, 1982)	0.64
" The marked decrease in the estimated absorption rate constant between phases 1 and 2 for each drug may have been due to slow dissolution of a large congealed mass of phenytoin and primidone in the gut."	( Acute phenytoin and primidone intoxication: a pharmacokinetic analysis. Cloyd, JC; Matzke, GR; Sawchuk, RJ, )	0.13
" It is shown for linear systems that if the absorption response and the response from an intravenous infusion or bolus administration are both well approximated by a polyexponential function, then the rate of absorption can be expressed as a sum of exponentials."	( An algorithm and computer program for deconvolution in linear pharmacokinetics. Veng-Pedersen, P, 1980)	0.26
" At each administration, extent of bioavailability, elimination rate constant, absorption rate constant, and volume of distribution of phenobarbital were calculated using a one-compartment open model."	( Bioavailability of phenobarbital by rectal administration. Higashi, A; Ikeda, T; Matsuda, I; Matsukura, M, 1981)	0.79
" The IP bioavailability of DEMIS (1."	( Dose-dependence and related studies on the pharmacokinetics of misonidazole and desmethylmisonidazole in mice. Workman, P, 1980)	0.26
"87 mmol/kg) of 2-14C-MAN or 2-14C-AN to male F344 rats, both chemicals were well absorbed from the GI tract and distributed to all major tissues."	( Comparative metabolism and disposition of acrylonitrile and methacrylonitrile in rats. Ahmed, AE; Burka, LT; Ghanayem, BI; Sanchez, IM, 1994)	0.29
" The switch to oral agents must take into consideration the differences in potency, half-life, and oral bioavailability between the agents."	( Outpatient therapy of iatrogenic drug dependency following prolonged sedation in the pediatric intensive care unit. Deshpande, JK; Gregory, DF; Tobias, JD, 1994)	0.29
" These findings also suggest that the bioavailability of praziquantel could be altered to a significant extent in humans taking drugs that are phenobarbital type inducers."	( Effects of phenobarbital and 3-methylcholanthrene pretreatment on the pharmacokinetics of praziquantel in rats. Hasler, JA; Masimirembwa, CM; Naik, YS, )	0.72
" Protein binding of PB was unchanged in ET-treated animals, but the extent of bioavailability of PB tended to increase."	( Toxicokinetics of phenobarbital in rats with DL-ethionine-induced liver injury. Fukushima, T; Kawai, Y; Kuwamura, Y; Noguchi, M; Tanaka, K, 1993)	0.62
" The absorption rate constant (Ka), apparent steady state volume of distribution (Vdss/F), and apparent total clearance (CL/F) were computed with the APIS software using blood level profiles from 34 patients divided into four groups: patients receiving either CBZ-CO or CBZ-CR in monotherapy, or CBZ-CO or CBZ-CR in comedication with PB."	( Steady state pharmacokinetics of carbamazepine-phenobarbital interaction in patients with epilepsy. Barra, Y; Bonneton, J; Genton, P; Iliadis, A; Mesdjian, E; Sennoune, S, 1996)	0.55
"A three-way crossover study with seven healthy male volunteers was conducted to determine the relative bioavailability of phenobarbital after single dose administration of 100 mg of phenobarbital as oral solution in Myvacet 9-08, and as a suspension, compared with a 100 mg phenobarbital tablet."	( Oral bioavailability of phenobarbital: a comparison of a solution in Myvacet 9-08, a suspension, and a tablet. Bosch, FH; Essink, GW; Lankhaar, G; van Sorge, AA; Yska, JP, 2000)	0.82
"The quantitative structure-bioavailability relationship of 232 structurally diverse drugs was studied to evaluate the feasibility of constructing a predictive model for the human oral bioavailability of prospective new medicinal agents."	( QSAR model for drug human oral bioavailability. Topliss, JG; Yoshida, F, 2000)	0.31
" This study will be helpful in providing clues about factors influencing the bioavailability of CDRI-85/92 as well as drug-drug interactions."	( Metabolism of CDRI-85/92, a new potent anti-ulcer agent, involving cis-trans conversion. Dikshit, DK; Gupta, RC; Lal, J; Madhusudanan, KP; Sharma, P; Srivastava, P, 2004)	0.32
" Human oral bioavailability is an important pharmacokinetic property, which is directly related to the amount of drug available in the systemic circulation to exert pharmacological and therapeutic effects."	( Hologram QSAR model for the prediction of human oral bioavailability. Andricopulo, AD; Moda, TL; Montanari, CA, 2007)	0.34
" time curve, apparent elimination half-life, and bioavailability of zonisamide."	( Pharmacokinetics of zonisamide and drug interaction with phenobarbital in dogs. Egashira, N; Fujiwara, M; Fukunaga, K; Matsuo, E; Mishima, K; Muto, M; Orito, K; Saito, M; Takikawa, S, 2008)	0.59
" Results of our work suggest that P-glycoprotein (P-gp) overexpression by repetitive seizures induced by MP administration does not modify brain bioavailability of carbamazepine."	( Differential hippocampal pharmacokinetics of phenobarbital and carbamazepine in repetitive seizures induced by 3-mercaptopropionic acid. Girardi, E; Gonzalez, NN; Höcht, C; Lazarowski, A; Mayer, MA; Opezzo, JA; Taira, CA, 2009)	0.61
" SCY-635 was shown to be orally bioavailable in multiple animal species and produced blood and liver concentrations of parent drug that exceeded the 50% effective dose determined in the bicistronic con1b-derived replicon assay."	( SCY-635, a novel nonimmunosuppressive analog of cyclosporine that exhibits potent inhibition of hepatitis C virus RNA replication in vitro. Erdmann, F; Fischer, G; Harris, R; Hopkins, S; Huang, Z; Murray, MG; Ribeill, Y; Scorneaux, B; Smitley, C; Wring, S, 2010)	0.36
"Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall elimination (Fg), and fraction escaping hepatic elimination (Fh)."	( Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination. Chang, G; El-Kattan, A; Miller, HR; Obach, RS; Rotter, C; Steyn, SJ; Troutman, MD; Varma, MV, 2010)	0.36
"2-(4-(4-(tert-Butylcarbamoyl)-2-(2-chloro-4-cyclopropylphenylsulfonamido)phenoxy)-5-chloro-2-fluorophenyl)acetic acid (AMG 853) is an orally bioavailable and potent dual antagonist of the D-prostanoid and chemoattractant receptor-homologous molecule expressed on T helper 2 cells receptors."	( Predicting the drug interaction potential of AMG 853, a dual antagonist of the D-prostanoid and chemoattractant receptor-homologous molecule expressed on T helper 2 cells receptors. Amore, BM; Banfield, C; Boudreaux, MD; Davis, JA; Emery, MG; Foti, RS; Pearson, JT; Prokop, SP; Rock, DA; Wahlstrom, JL; Wienkers, LC; Wong, SL; Zalikowski, JA, 2012)	0.38
" The objective of this study is to characterize the absolute bioavailability of phenobarbital in neonates and young infants, a pharmacokinetic parameter which has not yet been investigated."	( Pharmacokinetics and absolute bioavailability of phenobarbital in neonates and young infants, a population pharmacokinetic modelling approach. Boulamery, A; Brevaut-Malaty, V; Bruguerolle, B; Marsot, A; Simon, N; Vialet, R, 2014)	0.88
" In the present study, we compared bioavailability of phenobarbital after single dose administration of Luminal(®) vet vs."	( Is switching from brand name to generic formulations of phenobarbital associated with loss of antiepileptic efficacy?: a pharmacokinetic study with two oral formulations (Luminal(®) vet, Phenoleptil(®)) in dogs. Bankstahl, JP; Bankstahl, M; Löscher, W, 2013)	0.88
" The relative bioavailability of the two products (Phenoleptil(®) vs."	( Is switching from brand name to generic formulations of phenobarbital associated with loss of antiepileptic efficacy?: a pharmacokinetic study with two oral formulations (Luminal(®) vet, Phenoleptil(®)) in dogs. Bankstahl, JP; Bankstahl, M; Löscher, W, 2013)	0.64
" Thus, the reasons for the anecdotal reports, if true, that switching from the brand to the generic formulation of phenobarbital may lead to recurrence of seizures are obviously not related to a generally lower bioavailability of the generic formulation, although single dogs may exhibit lower plasma levels after the generic formulation that could be clinically meaningful."	( Is switching from brand name to generic formulations of phenobarbital associated with loss of antiepileptic efficacy?: a pharmacokinetic study with two oral formulations (Luminal(®) vet, Phenoleptil(®)) in dogs. Bankstahl, JP; Bankstahl, M; Löscher, W, 2013)	0.85
" No information is available concerning parenteral bioavailability of phenobarbital when induration develops at the injection or infusion site."	( Induration at Injection or Infusion Site May Reduce Bioavailability of Parenteral Phenobarbital Administration. Akabane, A; Echizen, H; Kato, T; Nakayama, H; Ogawa, R; Orii, T, 2017)	0.91
" Assuming that systemic clearance was constant in our patients, changes in the C/D ratio would have contributed to 40% (median) reduction in bioavailability of the drug from the injection or infusion site."	( Induration at Injection or Infusion Site May Reduce Bioavailability of Parenteral Phenobarbital Administration. Akabane, A; Echizen, H; Kato, T; Nakayama, H; Ogawa, R; Orii, T, 2017)	0.68
"Our data suggest that absolute bioavailability of phenobarbital may be reduced when induration develops at the injection or infusion site in patients treated parenterally by continuous subcutaneous infusion or intramuscular injection."	( Induration at Injection or Infusion Site May Reduce Bioavailability of Parenteral Phenobarbital Administration. Akabane, A; Echizen, H; Kato, T; Nakayama, H; Ogawa, R; Orii, T, 2017)	0.93
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."	( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019)	0.51
" Co-administration of PB with CsA resulted in significant decreases in the oral bioavailability of CsA though both the first pass and elimination phases."	( Interaction of cyclosporine with phenobarbital in cats: a preliminary study. Fukui, D; Hoshino, Y; Inden, T; Katayama, M; Otaka, R; Satoh, H, 2019)	0.8

Dosage Studied

Phenobarbital is a better discriminant when dosing is every 24 hours as with artesunate, rather than the 8-hourly regimen for quinine-tetracycline. Rats receiving phenobarbitals had therapeutic concentrations during most of the 24-hour dosing period, but also experienced supratherapeutic peak concentrations.

Excerpt	Relevance	Reference
" The one statistically significant interaction found was that in which phenytoin dosage decreased plasma carbamazepine concentrations."	( Interactions between anticonvulsants. Eadie, MJ; Lander, CM; Tyrer, JH, 1975)	0.25
"0 g of salicylamide administered to NV; thus, this dosage was used in the present study."	( Salycylamide glucuronide formation in liver disease and its change by drugs. Adachi, Y; Wakisaka, G; Yamamoto, T, 1975)	0.25
" During therapy with sulphasalazine, determination of acetylator phenotype and total sulphapyridine concentration can guide effective dosage and avoid side-effects."	( Clinical pharmacokinetics of sulphasalazine. Das, KM; Dubin, R, )	0.13
" Therefore, monitoring treatment by dosage adjustment alone is of little value."	( Plasma level monitoring of antipsychotic drugs. Cooper, TB, )	0.13
" The authors draw attention to the fact that there was a concomitant improvement in the behaviour of some patients and a diminution of maintainence dosage in relation to a previously published trial."	( [Re-evaluation of barbexaclone in 20 epileptic patients]. de Lima, JM; Fernandes, I; Oliveira, C, 1978)	0.26
" Phenytoin dosage was increased to study the effect on the frequency of seizures and the serum concentrations of phenytoin and phenobarbitone."	( Therapeutic and pharmacokinetic effects of increasing phenytoin in chronic epileptics on multiple drug therapy. Johnson, RH; Lambie, DG; Nanda, RN; Shakir, RA, 1976)	0.26
" The results were used to calculate the plasma levels of phenytoin in relation to dosage and to measure the effect of the simultaneous use of phenobarbital on the phenytoin plasma levels and of primidone together with phenobarbital on phenytoin concentration."	( In vivo interaction of anticonvulsant drugs. The mathematical correlation of plasma levels of anticonvulsant drugs in epileptic patients. Abarbanel, J; Eylath, U; Herishanu, Y; Rosenberg, P, 1978)	0.46
"Gamma hydroxybutyrate (GHB) was administered intravenously to monkeys that had been pretreated orally for 2 weeks with various anticonvulsant drugs or with L-DOPA at different dosage levels."	( Gamma hydroxybutyrate in the monkey. II. Effect of chronic oral anticonvulsant drugs. Snead, OC, 1978)	0.26
"The optimal dosage of phenytoin can be accurately determined by a pharmacokinetic method."	( Rapid metabolism of phenytoin: a method of calculating proper dosage. Allen, JP; Hawkins, DW; Hoffman, SF; Ludden, TM, 1979)	0.26
" It was found that: (1) a single dose of phenytoin suspension or capsules (5mg/kg/day) produced inadequate serum levels 16 and 24 hours after ingestion, and for this reason single dosage is not recommended; (2) twice-daily dosage of phenytoin suspension or capsules (5mg/kg/day) produced adequate serum levels in most children throughout the 24 hours, and this dosage is recommended; (3) 12 children continued to have seizures but when the dose was increased to 10mg/kg/day six of the 12 obtained control of seizures; (4) phenytoin reached equilibrium in the serum in five days provided the child had not previously been taking phenobarbitone; (5) of 13 children who had been taking phenobarbitone, 10 did not achieve equilibrium of phenytoin in serum for one to four weeks; (6) phenytoin suspension given twice-daily produced satisfactory serum levels provided the bottle was shaken well before dispensing; (7) apart from minor variations, phenytoin maintained its level in serum during the 14 to 30 months follow-up period, whether 5mg or 10mg/kg/day of phenytoin was given."	( Phenytoin serum levels in children with epilepsy: a micro immuno-assay technique. Broughton, PM; Forsythe, WI; Prendergast, MP; Toothill, C, 1979)	0.26
" By administering the phenobarbital as an initial single loading dose and closely monitoring the blood levels, maintenance dosing could easily be adjusted for variables in infant metabolism and pharmacologic effect."	( Management of neonatal narcotic abstinence utilizing a phenobarbital loading dose method. Finnegan, LP; Hopkins, LE; Mitros, TF, 1979)	0.82
" Prior dosing with phenobarbitone augments CCl4 toxicity only in the adult and the newborn but the foetus continues to be resistant."	( Diverse mechanisms of hepatocellular injuries due to chemicals: evidence in rats administered carbon tetrachloride or dimethylnitrosamine. Chopra, P; Das, PK; Dhar, A; Nayak, NC, 1975)	0.25
" Treatment with 25 OH CC in high dosage brought about clinical, radiological and laboratory cure of osteomalacia in both cases, reducing the frequency of fits in the epileptic patient."	( [4 cases of osteomalacia during anticonvulsant or sedative treatment]. Alcalay, M; Amor, B; Bontoux, D; Cayla, J; Charbonnier, A; Mery, C; Miravet, L; Rondier, J, 1975)	0.25
" This dose-response relationship suggests that (1) REM pressure was an indicator of a process that mediated the antidepressant effects of REM sleep deprivation, and (2) since improvement varied with stimulation of REM sleep, an unknown stimulus of REM sleep is a naturally occurring, endogenous antidepressant."	( Endogenous depression improvement and REM pressure. Barker, K; McAbee, R; Thurmond, A; Vogel, GW, 1977)	0.26
" The "specific" use of each drug on the various forms of epileptic seizures is determined and the possibility of crisis control with reduction of the drugs dosage is verified."	( [Effect of drugs on electroclinical types of epileptic seizures in Lennox-Gastaut syndrome]. Lison, MP; Speciali, GG, 1977)	0.26
" They demonstrate that taurocholate synthesis is increasing rapidly during the final stages of gestation and show that cortisol augments taurocholate synthesis in a dose-response pattern."	( Synthesis of taurocholate by rat fetal liver in organ culture: effects of cortisol in vitro. Graham, TO; Lester, R; Little, JM; Van Thiel, DH, 1979)	0.26
" The inability of several anxiolytic compounds to show activity at high doses prompted an investigation of the effect on corticosteroid levels of these drugs over a wider dosage range."	( The effect of various doses of minor tranquilizers on plasma corticosteroids in stressed rats. Barsuhn, C; Lahti, RA, 1975)	0.25
" Estrogens should be prescribed to relieve these symptoms specifically, and in the lowest dosage for the shortest time."	( Estrogen and alternative therapy of the menopausal patient. Lichten, EM, 1978)	0.26
" Liver and kidney samples were also taken at appropriate times after dosing and examined histologically for evidence of drug induced damage."	( Young Scientists Award Lecture 1977: An investigation into the value of some clinical biochemical tests in the detection of minimal changes in liver morphology and function in the rat. Clampitt, RB, 1978)	0.26
" If the patient has an active seizure disorder, prednisone dosage should be maintained at a higher level."	( Allograft survival in patients receiving anticonvulsant medications. Ettenger, RB; Fine, RN; Malekzadeh, MH; Pennisi, AJ; Uittenbogaart, CH; Wassner, SJ, 1977)	0.26
" Rats received phenobarbital- or barbital-admixed food on a graded-increase dosage schedule over 30-40 days."	( Experimental barbiturate dependence. I. Barbiturate dependence development in rats by drug-admixed food (DAF) method. Izumi, T; Tagashira, E; Yanaura, S, 1978)	0.61
" This new dissolution tester possibly can be useful in determining drug release from solid dosage forms and correlating it with in vivo bioavailability because dissolution rate can be controlled easily with the adjustment of air pressure without complicated changes in the apparatus, there is no excessive settling of particles, and complete drug dissolution can be achieved with no clogging of the screen."	( New in vitro dissolution test apparatus. Nasir, SM; Nasir, SS; Wilken, LO, 1979)	0.26
" The plasma level/dosage ratio has been found to have a highly significant correlation with the age of the patient both for dosage in mg/kg and in mg/m2."	( Correlation between age and plasma level/dosage ratio for phenobarbital in infants and children. Nino, LM; Principi, N; Rossi, LN, 1979)	0.5
"A very easy, reliable and specific gas-chromatographic method for identification and dosage of 11 barbiturates in plasma is presented."	( Routine identification and determination of 11 barbiturates in biological samples. Faure, J; Feuerstein, C; Gavend, M; Vincent, F, 1979)	0.26
" Dosage supplements required can be calculated from the postinfusion rate of fall of serum phenobarbital."	( Intravenous phenobarbital therapy in barbiturate and other hypnosedative withdrawal reactions: a kinetic approach. Bhushan, CM; Kapur, BM; Martin, PR; Sellers, EM; Whiteside, EA, 1979)	0.86
"Amount of water ingested, total laps, duration of drinking, amount per lap, laps per minute, and running velocity were investigated as a function of phenobarbital dosage (0 to 60 mg/kg)."	( The effect of phenobarbital dose upon a variety of drinking related response measures. Schmidt, H, 1979)	0.82
" The majority of the patients receiving Comital-L tablets showed low serum levels of phenytoin and high serum levels of phenobarbital, while patients treated with the usual daily dosage of Hydantol-F tablets showed adequate therapeutic serum levels of both phenytoin and phenobarbital."	( Serum levels of phenytoin and phenobarbital in epileptic patients treated with mixture antiepileptic tablets, Comital-L or Hydantol-F. Hattori, M; Kazamatsuri, H, 1979)	0.76
"The effect of dosage schedules on plasma drug levels was evaluated in two groups of ambulant epileptic patients, whose treatment with diphenylhydantoin (DPH) or phenobarbital (PB) had been simplified by reducing the daily frequency of the dosage regimens."	( Effectiveness of simplified dosage schedules on the management of ambulant epileptic patients. Galli, A; Zaccara, G, 1979)	0.46
" The animals were made physically dependent by 5 weeks of twice daily "maximally tolerable" sodium pentobarbital dosing intragastrically."	( Evaluation of anticonvulsants in barbiturate withdrawal. Boisse, NR; Okamoto, M; Rosenberg, HC, 1977)	0.26
" the first dosing period was 42 dyas (6 weeks) in which drugs were repeatedly administered orally once daily, followed by a withdrawal period (7 days), the second dosing period was continued from the 50th-78th day in which the form and schedule of drug administration was as in the first dosing period."	( [Studies on the physical dependence liability of chlorphenesin carbamate (author's transl)]. Aihara, H; Saito, S; Sasajima, M; Tanaka, Y; Tarumoto, Y, 1977)	0.26
" The blood proportional to the dosage per kilogram, and was not related to weight or gestational age."	( Phenobarbital dosage for control of neonatal seizures. Kriel, R; Lockman, LA; Thompson, T; Virnig, N; Zaske, D, 1979)	1.7
" Further, the oxidation of D-glucuronolactone is also enhanced by phenobarbital in all rats without a genetic predisposition, and its dose-response curve is very similar to that of the low-Km aldehyde dehydrogenase."	( Inducible aldehyde dehydrogenases in the hepatic cytosol of the rat. Marselos, M; Nousiainen, U; Törrönen, R, 1977)	0.49
" Serum levels of phenobarbital were determined for 21 days after dosing by means of radioimmunoassay."	( Bioavailability of oral and intramuscular phenobarbital. Booker, HE; Viswanathan, CT; Welling, PG, )	0.74
"The reported interaction of griseofulvin with phenobarbital was studied in the rat following oral administration of different dosage forms."	( Griseofulvin---phenobarbital interaction: a formulation-dependent phenomenon. Axelson, JE; Jamali, F, 1978)	0.87
"The presence and mechanism of synergism of action between ethanol and amylobarbitone, phenobarbitone or methaqualone was determined by application of simple pharmacokinetic models to log dose-response curves and plasma concentration-time curves for the hypnotics alone or when ethanol was given concurrently."	( Interaction of ethanol with amylobarbitone, phenobarbitone and methaqualone. Reavey, PC; Tilstone, WJ, 1978)	0.26
" Dose-response curves were obtained using mice at pressures ranging from 1 to 125 atm for five agents, namely alpha-chloralose, ethylcarbamate, phenobarbital and, for comparison, nitrogen and argon."	( The pressure reversal of a variety of anesthetic agents in mice. Miller, KW; Wilson, MW, 1978)	0.46
"Ambulant patients with recently diagnosed generalised or psychomotor seizure disorders or both were randomly assigned to two dosage regimens of phenytoin."	( Phenytoin dosage in ambulant epileptic patients. Alberts, M; Terrence, C, 1978)	0.26
"Theophylline bioavailability following chronic dosing of an elixir and two commercial tablet formulations (I and II) relative to an acute dose of elixir was evaluated in healthy volunteers."	( Theophylline bioavailability following chronic dosing of an elixir and two solid dosage forms. Azarnoff, DL; Fixley, M; Shen, DD, 1978)	0.26
" Furthermore, usual increase in the activity of drug biotransformation enzymes seen after phenobarbital treatment appears to decrease in rats dosed with this funaicide."	( Toxicologic studies of N-trichloromethylthio-4-cyclohexene-1,2-dicarboximide (captan): its metabolism by rat liver drug-metabolizing enzyme system. Dalvi, RR; Peeples, A, 1978)	0.48
" Mean saliva phenytoin concentrations did not differ significantly between the two treatment settings and were low largely because of the low mean dosage prescribed."	( Compliance with anticonvulsant therapy in a hospital clinic and in the community. Dollery, CT; Mucklow, JC, 1978)	0.26
" Monitoring plasma concentrations may lead to adaptations of the choice of the drug and of the dosage regimen."	( Kinetics of drug interactions in the treatment of epilepsy. Guelen, P; Knop, H; Schobten, F; van der Kleijn, E; Vree, T; Westenberg, H, 1978)	0.26
"Phenobarbital is known to reduce serum bilirubin concentration in the newborn infant, but optimal dosage is unknown."	( Plasma concentrations of phenobarbital in mother and child after combined prenatal and postnatal administration for prophylaxis of hyperbilirubinemia. Boréus, LO; Jalling, B; Wallin, A, 1978)	2
"Minophylline (theophylline ethanoate of piperazine) and aminophylline (theophylline ethylenediamine) were determined spectrophotometrically in dosage forms without interference from excipients and/or preservatives."	( Spectrophotometric determination of theophylline formulations. Abdine, H; Elsayed, MA; Elsayed, YM, 1979)	0.26
" Blood levels of primidone decreased during pregnancy and rose postpartum requiring dosage adjustments."	( Carbamazepine levels in pregnancy and lactation. Blake, DA; Freeman, JM; Luff, RD; Niebyl, JR, 1979)	0.26
" Injection of an ovulation-blocking dosage of phenobarbital at 1345 h blocked the FSH rise."	( Simulation of the early phase of the proestrous follicle-stimulating hormone rise after infusion of luteinizing hormone-releasing hormone in phenobarbital-blocked rats. Blake, CA, 1976)	0.72
" The data indicate that the dosage regimen described is suitable for patients on oral phenytoin who have to be transferred to im drug for short periods."	( Oral and intramuscular phenytoin. Ramsay, RE; Wilder, BJ, 1976)	0.26
" Combined treatment with other anticonvulsant drugs decreases the half-life and more frequent dosing may be necessary."	( Clinical pharmacokinetics of anticonvulsants. Dam, M; Hvidberg, EF, 1976)	0.26
" (3) Use of well-standardized, yet simplified, mental performance tests in combination with changes in the dosage of medication can help in reaching a compromise between acceptable seizure control and avoidance of excessive slowing of mental activity."	( Effects of different dosages of anticonvulsant drugs on mental performance in patients with chronic epilepsy. Dekaban, AS; Lehman, EJ, 1975)	0.25
"This study was undertaken to determine the relationship of serum ACD levels to dosage in a group of patients who had been seizure free for at least two years."	( The relation of anticonvulsant drug levels to complete seizure control. Feldman, RG; Pippenger, CE, 1976)	0.26
" The study provided some indication that when eterobarb and phenobarbital were used in high dosage with corresponding high serum barbiturate levels (over 30 mug per milliliter), eterobarb had a superior therapeutic effect."	( Eterobarb therapy in epilepsy. Hanahan, E; Mattson, RH; Williamson, PD, 1976)	0.5
"The present study investigated order and temporal spacing interactions of phenytoin and phenobarbital in terms of plasma levels during multiple dosing in monkeys."	( Interactions of phenytoin and phenobarbital in terms of order and temporal spacing of administration in monkeys. Farquhar, JS; Levy, RH; Lockard, JS; Uhlir, V, 1976)	0.77
" It is suggested that reduction of methadone dosage in late pregnancy results in reduced incidence of withdrawal but must be carefully carried out."	( Observation and treatment of neonatal narcotic withdrawal. Chappel, JN; Davis, R; Gumpel, J; Madden, JD; Mejia, A; Zuspan, F, 1977)	0.26
" As expected, the chloramphenicol concentrations in the serum of the newborns was considerably higher than that of infants and small children with the same dosage of chloramphenicol."	( Studies on the concentrations of chloramphenicol in the serum and cerebrospinal fluid of neonates, infants, and small children. Reciprocal reactions between chloramphenicol, penicillin and phenobarbitone. Pringsheim, W; Windorfer, A, 1977)	0.26
"5 or 23 mmol/kg) and sacrificed 24 h after dosing exhibited liver toxicity."	( A study of the mechanism of halothane-induced liver necrosis. Role of covalent binding of halothane metabolites to liver proteins in the rat. Rao, GS, 1977)	0.26
" Daily dosing with acetaminophen for up to 3 weeks increased the rate of elimination of 14C from the blood after 4 h, and increased the urinary excretion of both total 14C and the glucuronide and sulfate conjugates."	( Effect of subacute dosing and phenobarbital and 3-methylcholanthrene pretreatment on the metabolism of acetaminophen in rats. Beaubien, AR; Thomas, BH; Zeitz, W, 1977)	0.55
"The kinetic parameters of indocyanine green elimination from blood were determined after an intravenous load of the dye in a dosage of 2-4 mg per kg body weight in 22 newborns with a non-hemolytic hyperbilirubinemia."	( [Indocyanine green kinetics in newborns with non-hemolytic hyperbilirubinemia (author's transl)]. Gladtke, E; Heimann, G; Roth, B, 1977)	0.26
" We conclude that theophylline dosage need not be altered during concomitant administration of phenobarbital."	( Effect of phenobarbital on the disposition of intravenous theophylline. Ogilvie, RI; Piafsky, KM; Sitar, DS, 1977)	0.88
" The low dosage of PB had no effect on SEPs except those recorded in the mesencephalic reticular formation; high dosage resulted in general SEP attenuation."	( Phenobarbital and phenytoin effects on somatosensory evoked potentials and spontaneous EEG in normal cat brain. Kaplan, BJ, 1977)	1.7
" Principal features of the complex results include: double peaks in the time course of convulsion thresholds (Pc); an early peak and a shoulder in the time course of pressures reversing anesthesia (Pa); far steeper dose-response curves for Pa than for Pc; selectively greater anticonvulsant effect for phenobarbital than for the other barbiturates; and enhancement of Pa with simultaneous depression of Pc by reserpine in phenobarbital-pretreated mice."	( Interaction of central nervous system effects of high pressures with barbiturates. Beaver, RW; Brauer, RW; Lahser, S, 1977)	0.43
" 4 In individual patients, within the limits of dosage studied, the relation between plasma phenobarbitone level and drug dose was not rectilinear if phenobarbitone itself was taken, but was rectilinear if methylphenobarbitone was taken."	( Factors influencing plasma phenobarbitone levels in epileptic patients. Eadie, MJ; Hooper, WD; Lander, CM; Tyrer, JH, 1977)	0.26
"A neonate treated initially with oxacillin intravenously for two weeks and who was receiving phenobarbital for a seizure disorder subsequently failed to achieve therapeutic levels of orally administered dicloxacillin, even when the dosage was as high as 175 mg/kg/day."	( Subtherapeutic dicloxacillin levels in a neonate: possible mechanisms. Hegyi, T; Schwartz, GJ; Spitzer, A, 1976)	0.48
"Adriamycin dosage should be reduced in patients with impaired liver function, since adriamycin disposition is influenced by liver metabolism and biliary excretion."	( Alterations in adriamycin efficacy by phenobarbital. Bachur, NR; Reich, SD, 1976)	0.53
"Mice dosed with methylmercury chloride (0."	( The effect of oral doses of a polythiol resin on the excretion of methylmercury in mice treated with cysteine, D-penicillamine or phenobarbitone. Clarkson, TW; Magos, L, 1976)	0.26
" Phenobarbital at plasma concentrations achieved by usual therapeutical dosage schedules of the drug does not interfere with the protein binding of phenprocoumon as could be shown by equilibrium dialysis."	( [Elimination kinetics of phenprocoumon (Marcumar) in liver cirrhosis and after premedication with phenobarbital]. Glogner, P; Heni, N; Lehnhardt, G, 1976)	1.38
"The addition of phenobarbitone in therapeutic dosage to the drug regimen of prednisolone-treated subjects with rheumatoid arthritis produced measurable deterioration in the clinical status of the patients associated with a more rapid clearance of prednisolone from plasma."	( Effects of enzyme induction on metabolism of prednisolone. Clinical and laboratory study. Brooks, PM; Buchanan, WW; Downie, WW; Grove, M, 1976)	0.26
" Dosage of each drug used in this experiment was calculated by determining the dosage which caused the same degree of muscle relaxation and sedative action in mice (see, Fig."	( [Conditioning of emotional behavior originating at the hypothalamus. (2) Effects of drugs on conflict-induced behavior models]. Abe, Y; Mineo, K; Yanaura, S, 1976)	0.26
" The risk of over dosage and the large individual variation in the metabolism of phenobarbitone in the new born lead us to recommend checking the blood levels when giving repeated doses."	( [Pharmacokinetic data on phenobarbital. Study on the influence of gestational age and dysmaturity]. Humbert, F; Mur, JM; Pladys, JC; Royer, RJ; Royer-Morrot, MJ; Vert, P, 1976)	0.56
" Subtherapeutic levels appear to be due to inadequate dosage adjustment."	( The necessity of drug level monitoring in anticonvulsant drug therapy. Bailey, DG; Davis, HL; Johnson, GE; Wilson, TW, 1976)	0.26
" The relation changed with age, the dosage requirement (on a day weight basis) tending to fall as patients grew older."	( The effects of phenobarbitone dose on plasma phenobarbitone levels in epileptic patients. Eadie, MJ; Hooper, WD; Lander, CM; Tyrer, JH, 1976)	0.26
" Use of homogenates from animals treated with 3-methylcholanthrene gave much more reproducible results in smoke fraction assays because larger numbers of revertants were obtained, and dose-response curves were linear over the range 25 to 250 mug condensate."	( Metabolism of cigarette smoke condensates by human and rat homogenates to form mutagens detectable by Salmonella typhimurium TA1538. Hackney, C; Hutton, JJ, 1975)	0.25
" Further, this scoring system has been used by relating it to the dosage schedule of phenobarbital or paregoric as part of an ongoing research project designed to test the comparative usefulness of recommended treatments for neonates with abstinence symptoms."	( Assessment and treatment of abstinence in the infant of the drug-dependent mother. Connaughton, JF; Emich, JP; Finnegan, LP; Kron, RE, 1975)	0.48
" In order to rapidly achieve therapeutic levels, it is suggested that a loading dose of 8 to 10 mg per kg be administered for 2 days followed by reduction of dosage to a maintenance level of 5 to 6 mg per kg with frequent monitoring of plasma phenobarbital concentrations."	( Phenobarbital plasma levels in neonates. Pippenger, CE; Rosen, TS, 1975)	1.88
" Dose-response curves can be derived for the parameters used for assessing dysfunction."	( Metabolic alterations in organ function. Plaa, GL, 1975)	0.25
" For the often seriously ill infants with convulsions it is therefore difficult to construct rational maintenance dose schedules, and optimal dosage must be based on repeated determinations of the plasma concentration."	( Plasma concentrations of phenobarbital in the treatment of seizures in newborns. Jalling, B, 1975)	0.56
" The rats (drug dependence-experimented rats) who survived the first stage of this experiment were continuously subjected to re-administration by the same dosage schedule as in Exp."	( [Comparison of development of drug dependence in naive and drug dependence-experienced rats]. Tagashira, E; Yanaura, S, 1975)	0.25
"Using isolated rat aortic strips (AS) and portal veins (PV), it was found that all of the barbiturates studied (thiopental, secobarbital, pentobarbital, amobarbital, phenobarbital, and barbital): a) inhibit development of spontaneous mechanical activity (vasomotion) in AS and PV in concentrations used to induce surgical anesthesia or concentrations used for anticonvulsive therapy; b) dose-dependent attenuate contractions induced by epinephrine and potassium (K+); c) cause non-competitive displacement of the dose-response curves of these vasoactive compounds; d) attenuate calcium (Ca++)-induced contractions of K+-depolarized AS and PV; e) rapidly relax drug-induced, as well as Ca++-induced, contractions of AS and PV."	( Barbiturates and aortic and venous smooth-muscle function. Altura, BM; Altura, BT, 1975)	0.45
" The presence of immunological defects was independent of the dosage of drug, its serum concentration, the duration of therapy and the sex of the subject."	( Depression of immune competence by phenytoin and carbamazepine. Studies in vivo and in vitro. Forbes, IJ; Sorrell, TC, 1975)	0.25
" --Must be given in relatively higher dosage to children on account of a faster catabolism."	( [Serum phenobarbital levels in epileptics]. Brachet, A; Henry, P; Loiseau, P, 1975)	0.71
" Methoxyflurane dosage was sufficiently low that renal abnormalities did not occur except in rats treated also with phenobarbital; these animals developed polyuria and the morphologic lesion typically associated with F--induced nephrotoxicity."	( A comparison of renal effects and metabolism of sevoflurane and methoxyflurane in enzyme-induced rats. Beppu, WJ; Cook, TL; Hitt, BA; Kosek, JC; Mazze, RI, )	0.34
" Physical dependence on phenobarbital and diazepam was produced using the same dosage schedules as with morphine."	( Physical dependence on morphine, phenobarbital and diazepam in rats by drug-admixed food ingestion. Suzuki, T; Tagashira, E; Yanaura, S, 1975)	0.84
"A daily dosage of 100 mg phenobarbitone administered orally to pregnant women for three days or more immediately before delivery has reduced the various mortality rates for low-birth-weight infants by 50% or more."	( Decrease in the mortality rates for low-birth-weight infants after phenobarbitone treatment. Trolle, D, 1976)	0.26
" Evaluation of dose-response curves revealed saturation phenomena."	( Expiratory measurement of maximal amino-pyrine demethylation in vivo: effect of phenobarbital, partial hepatectomy, protacaval shunt and bile duct ligation in the rat. Bircher, J; Lauterburg, BH, 1976)	0.48
" The resulting dose-response curve at pressure gave an ED50 that was 64 per cent larger than the ED50 at 1 atm."	( Pressure antagonism of barbiturate anesthesia. Eger, EI; Smith, M; Smith, RA; Winter, PM, 1976)	0.26
" Dose-response curves with and without phenobarbital pretreatment showed a constant 90% (1-log) reduction in the toxicity of cyclophosphamide to leukemic colony-forming units, whereas enzyme induction had no effect on the toxicity of the drug to normal bone marrow colony-forming units."	( The effect of phenobarbital on cyclophosphamide antitumor activity. Alberts, DS; van Daalen Wetters, T, 1976)	0.89
" The results were opposite to other studies, probably because the dose and dosing intervals were different."	( Effect of traditional Chinese herbal medicines on the pharmacokinetics of western drugs in Sprague-Dawley rats of different ages (II): Aminophylline-huan shao tan and aminophylline-pu chung yi chi tang. Chen, SM; Hou, SJ; Lin, SY; Perng, RI; Young, TK, 1992)	0.28
"The dose-response of phenobarbital (PB) promotion of hepatocarcinogenesis in rats was investigated."	( Threshold dose dependence in phenobarbital promotion of rat hepatocarcinogenesis initiated by diethylnitrosamine. Hayashi, Y; Maekawa, A; Matsushima, Y; Mitsumori, K; Ogasawara, H; Onodera, H, 1992)	0.89
" In a dose ranging study, adult male rats were treated daily for 4 days with phenobarbital (80 mg/kg, ip) and on the fifth day were dosed with 0, 2, 3, or 4 mmoles/kg, ip, bromobenzene."	( Potentiation of bromobenzene-induced pneumotoxicity by phenobarbital as determined by bronchoalveolar lavage fluid analysis. Carlson, GP; Day, BJ; DeNicola, DB, 1992)	0.76
" The acute or chronic administration of phenoxybenzamine alone displaced the dose-response curve to cirazoline to the right in a dose-dependent manner, while reducing the slope function and maximum response to the agonist."	( A comparison of the effects of acute versus chronic administration of phenoxybenzamine on pressor responses elicited by the selective alpha 1-adrenoceptor agonist cirazoline in the pithed rat preparation. Tabrizchi, R; Triggle, CR, 1992)	0.28
"Routine clinical pharmacokinetic data collected from patients receiving phenobarbitone have been analysed to evaluate the role of patient characteristics for estimating dosing regimens."	( Phenobarbitone population pharmacokinetics from routine clinical data: role of patient characteristics for estimating dosing regimens. Aoyama, T; Higuchi, S; Yukawa, E, 1992)	0.28
"To report unusually high theophylline dosing requirements in a smoker receiving concomitant therapy with phenytoin and phenobarbital."	( Massive theophylline dosing in a heavy smoker receiving both phenytoin and phenobarbital. Basile, SA; Cury, JD; Nicholson, JP, 1992)	0.72
"The additive influence of smoking, phenytoin, and phenobarbital greatly increased the theophylline dosing requirements."	( Massive theophylline dosing in a heavy smoker receiving both phenytoin and phenobarbital. Basile, SA; Cury, JD; Nicholson, JP, 1992)	0.77
" Maintenance dosage adjustments, when necessary, were based on serial plasma concentrations of the drug, sustained at between 5 and 30 micrograms/ml."	( Phenobarbital in the prophylaxis of late posttraumatic seizures. Arrigo, A; Bonuccelli, U; Murri, L; Parenti, G; Rossi, G, 1992)	1.73
" Regular 2 weekly follow up for a minimum period of 2 months was done, after altering the drug dosage and bringing plasma level(s) within therapeutic range."	( "An analysis of epileptic patients nonresponsive to drugs". Joshi, MV; Karande, SC; Kshirsagar, NA; Shah, PU, 1992)	0.28
" There was no calcitonin correlation with the anticonvulsant dosage or with the total doses ingested."	( Long-term influence of anticonvulsant agents on calcitonin, parathyroid hormone and osteocalcin. Arias, JA; Cabranes, JA; Rico, H; Varela de Seijas, E, 1992)	0.28
" Upon a chlorpromazine minimal effective dose reduction, target behaviors increased and dosage was returned to prior levels with the conclusion that chlorpromazine was controlling the target behaviors."	( A case of phenobarbital exacerbation of a preexisting maladaptive behavior partially suppressed by chlorpromazine and misinterpreted as chlorpromazine efficacy. Hanzel, TE; Harder, SR; Kalachnik, JE, 1992)	0.69
" Pharmacokinetic dose prediction methods have been developed allowing individual dosage adaptation."	( Therapeutic drug monitoring and pharmacokinetic dose prediction methods. Oellerich, M, 1992)	0.28
" The significant decrease in half-life after repeated dosing with phenobarbital may be indicative of enzyme induction."	( Pharmacokinetics of phenobarbital in horses after single and repeated oral administration of the drug. Knox, DA; Krista, LM; Nostrandt, AC; Pedersoli, WM; Ravis, WR; Schumacher, J; Spano, JS, 1992)	0.84
" At the highest dosage tested, loratadine was less effective than phenobarbital as an inducer of 2B1 and 2B2, although the induction of these proteins could be detected immunochemically even at the lowest dosage of loratadine tested."	( Evaluation of loratadine as an inducer of liver microsomal cytochrome P450 in rats and mice. Casciano, CN; Cayen, MN; Clement, RP; Parkinson, A, 1992)	0.52
" In fact, the response to PB-type inducers in male or female Zucker rats is probably most clearly explained as a shift of the dose-response curve sharply to the right (decreased responsiveness, compared to F344/NCr or DA rats of the same sex)."	( A markedly diminished pleiotropic response to phenobarbital and structurally-related xenobiotics in Zucker rats in comparison with F344/NCr or DA rats. Devor, DE; Diwan, BA; Dragnev, KH; Jones, CR; Lubet, RA; Miller, MS; Nims, RW; Rice, JM; Ward, JM, 1992)	0.54
" A linear relationship was observed between the dosage of BB administered and BB-GSH excreted into bile, up to a dosage of 250 mumol/kg of BB."	( Bromobenzene-glutathione excretion into bile reflects toxic activation of bromobenzene in rats. Klaassen, CD; Madhu, C, 1992)	0.28
" All of the available serum phenobarbital concentrations and dosage amounts were fitted with least-squares nonlinear regression analysis to a 1-compartment model."	( Phenobarbital pharmacokinetics in obesity. A case report. Danziger, LH; Rodvold, KA; Wilkes, L, 1992)	2.02
" doses of phenobarbital (50 mg/kg) or saline, were orally dosed with carbon tetrachloride (0."	( Effect of phenobarbital treatment on carbon tetrachloride-mediated cytochrome P-450 loss and diene conjugate formation. Moody, DE, 1992)	1.09
" We report the elevated excretion of D-glucaric acid (DGA) and D-glucuronic acid (GCA) following treatment with 2,7-difluorospirofluorene-9,5'-imidazolidine-2'4'-dione (Imirestat, IM, Al 1576, HOE 843) at 50 mg/kg/day for 1 month, but not with 3-4-bromo-2-fluorobenzyl-4-oxo-3-phthalazine-1-ylacetic acid (Ponalrestat, Statil), dosed at 50 mg/kg/day for 2 weeks."	( Studies on the biochemical effects of the aldose reductase inhibitor 2,7-difluorospirofluorene-9,5'-imidazolidine-2',4'-dione (Al 1576, HOE 843). Detection of D-glucaric and D-glucuronic acid excretion by high resolution 1H and 13C NMR spectroscopy. Gilbert, PJ; Hoyle, VR; Nicholson, JK; Troke, JA; Vose, CW, 1992)	0.28
" Following ip dosing of the mouse with the phenobarbital N-glucosides, free phenobarbital could be detected in the urine."	( Identification of phenobarbital N-glucosides as urinary metabolites of phenobarbital in mice. Agriesti, BE; England, TM; Ferkany, JW; Soine, PJ; Soine, WH, 1991)	0.88
" An apparatus was constructed to allow agonist dose-response curves to be determined at high pressures using voltage-clamped oocytes."	( Effects of general anesthetics and pressure on mammalian excitatory receptors expressed in Xenopus oocytes. Daniels, S; Inman, N; Price, DJ; Shelton, CJ; Smith, EB; Zhao, DM, 1991)	0.28
" Female Sprague-Dawley rats were orally dosed with mirex (12."	( Mirex exposure inhibits the uptake of estradiol-17 beta(beta-D-glucuronide), taurocholate, and L-alanine into isolated rat hepatocytes. Teo, S; Vore, M, 1990)	0.28
" All studied drugs proved to be safe at the administered dosage with regard to their influence on cerebral hemodynamics in very immature infants."	( Cerebral hemodynamics in perinatal pharmacology. Jorch, G; Rabe, H, 1991)	0.28
" Laboratory measurements of phenobarbital and methadone helped to identify the use of illicit methadone, as well as incorrect self-administration, such as the consumption of several days' dosage at one time."	( Measuring compliance in methadone maintenance patients: use of a pharmacologic indicator to "estimate" methadone plasma levels. Calvert, R; Feely, M; Hay, A; Raistrick, D; Wolff, K, 1991)	0.58
" Serum concentrations differed even with the same dosage among individual dogs."	( [Effectiveness of bromide in therapy resistant epilepsy of dogs]. Jürgens, U; Schwartz-Porsche, D, 1991)	0.28
" There was no difference in NADPH-cytochrome c reductase or 7-ethoxyresorufin-O-deethylase (EROD) activity between ewes, control lambs and phenobarbitone-dosed lambs 3 weeks after dosing ceased."	( Microsomal enzymes in lambs and adult sheep, and their possible relationship to alveld. Flåøyen, A; Jensen, EG, 1991)	0.28
" These studies showed clearly that styrene inhalation induced principally cytochrome P450IE1, whereas styrene given by gavage at a high narcotic dosage induced both P450IIE1 (NDMAD, 60%) and P450IIB (PROD, 3000%)."	( Metabolism of inhaled styrene in acetone-, phenobarbital- and 3-methylcholanthrene-pretreated rats: stimulation and stereochemical effects by induction of cytochromes P450IIE1, P450IIB and P450IA. Elovaara, E; Engström, K; Gelboin, HV; Nakajima, T; Park, SS; Vainio, H, 1991)	0.54
" In order to use these effectively, the critical care nurse must be aware of the indications and controversies surrounding their use, the patho-physiologic conditions that impact on the disposition, and appropriate dosing and monitoring of these agents in the critical care setting."	( Anticonvulsants: pharmacotherapeutic issues in the critically ill patient. Dupuis, RE; Miranda-Massari, J, 1991)	0.28
" Tolerance to MES was not apparent after 5 days of oral daily dosing of remacemide."	( Preclinical profile of remacemide: a novel anticonvulsant effective against maximal electroshock seizures in mice. Becker, CN; Frankenheim, JM; Garske, GE; Gentile, RJ; Griffith, RC; Napier, JJ; Ordy, JM; Palmer, GC; Stagnitto, ML; Woodhead, JH, )	0.13
"We used a pharmacokinetically derived phenobarbital dosing protocol to treat alcohol withdrawal syndrome in patients admitted to a family medicine inpatient service."	( Pharmacokinetic dosing of phenobarbital in the treatment of alcohol withdrawal syndrome. Gwyther, RE; Ives, TJ; Mooney, AJ, 1991)	0.85
" Phenytoin (PHT) dosage had to be increased in 85% of pregnancies in which the drug was received, carbamazepine (CBZ) dosage in 70%, and phenobarbital (PB) or methylphenobarbital (MPB) dosage in 85%, in an attempt to prevent or correct a fall in plasma concentrations of the respective drugs as pregnancy progressed."	( Plasma antiepileptic drug concentrations during pregnancy. Eadie, MJ; Lander, CM, )	0.33
" Four-day-old female F344/N rats were dosed with diethylnitrosamine (10 mg/kg)."	( Effects of alpha-tocopherol, phenobarbital, and butylated hydroxyanisole during promotion of diethylnitrosamine-initiated rat hepatocarcinogenesis. Duitsman, P; Hendrich, S; Jackson, A; Krueger, SK; Myers, RK, 1991)	0.57
" Based on our experience with this case, several recommendations are provided regarding management of drug intoxications with charcoal-sorbitol suspension, including meticulous attention to fluid-electrolyte balance, type of replacement fluid, and dosing of the suspension."	( Hypernatremia due to repeated doses of charcoal-sorbitol. Allerton, JP; Strom, JA, 1991)	0.28
" Comparison with the single dosing showed no marked alterations in absorption, distribution, metabolism and excretion."	( Pharmacokinetics of 4-acetylaminophenylacetic acid. 2nd communication: tissue accumulation and enzyme induction in rats after repeated administration, and placental and milk transfer after single dosing. Iida, S; Morino, A; Nomura, A; Sugihara, K; Sugiyama, M, 1990)	0.28
" These findings should therefore be considered when defining dosage regimens or interpreting serum drug concentrations."	( Analysis of the factors influencing anti-epileptic drug concentrations--valproic acid. Aoyama, T; Higuchi, S; Hirata, K; Ieiri, I; Yamada, H, 1990)	0.28
" Male Sprague-Dawley rats were pretreated with three daily ip doses of phenobarbital (50 mg/kg) or saline and then orally dosed with CCl4 (2."	( Phenobarbital pretreatment alters the localization of CCl4-induced changes in rat liver microsomal fatty acids. James, JL; Moody, DE; Smuckler, EA, 1990)	1.95
" A graded dose-response relationship was found between PB treatment and most but not all parameters."	( Drug metabolizing capacity in vitro and in vivo--II. Correlations between hepatic microsomal monooxygenase markers in phenobarbital-induced rats. Houston, JB; Matthew, DE, 1990)	0.49
" The precision of the dosage with this method meets the requirements of the European Pharmacopeia."	( [The use of a cupric derivative of triazene n-oxide for volumetric analysis of phenobarbital]. Balkadjian, M; Eder, H; Tronchet, JM; Zosimo-Landolfo, G, 1990)	0.51
" On investigating the dose response curve for tumour promotion one finds that hepatocellular carcinomas only appear at a high dosage of phenobarbital and it seems likely that the human exposure to inducers in food, and in therapy with anticonvulsants, is in the dosage range well below that which causes promotion of liver cancer."	( Nutrition and enzyme inducers in liver tumor promotion in human and rat. Driver, H; McDanell, R; McLean, EM, 1990)	0.48
" Comparison of the dose-response curves of the in vivo and in vitro assays indicated that urinary metabolites of lindane provided a good index of phenobarbital-induced change in both phase I and phase II reactions."	( Comparison of in vivo and in vitro methods for assessing the effects of phenobarbital on the hepatic drug-metabolizing enzyme system. Carlson, GP; Chadwick, RW; Copeland, MF; Most, BM; Trela, BA, 1985)	0.7
" Dose-response experiments showed that the hepatocarcinogenic effects of long-term chlordecone administration became undetectable at concentrations in non-initiated rat liver in the same range as those measured in human biopsies taken from exposed workers who exhibited no liver effects."	( Evaluation of chlordecone in a two-stage model of hepatocarcinogenesis: a significant sex difference in the hepatocellular carcinoma incidence. Blanke, RV; Fitzgerald, R; Guzelian, PS; Sirica, AE; Wilkerson, CS; Wu, LL, 1989)	0.28
" The technique is simple and rapid: 4 anticonvulsants are simultaneously extracted and dosed, valproic acid, only has to be dosed lonely."	( [Plasma determination of 7 common drugs by high performance liquid chromatography]. Baty, C; Jambou, J; Leducq, B; Richard, L, 1989)	0.28
" When the drug was repeatedly coadministered with DPH or CBZ, the initial VPA elimination from plasma up to 1 h after dosing was less than with VPA alone, while PB significantly enhanced the disappearance of VPA."	( Effects of anticonvulsants on plasma levels and entero-hepatic circulation of valproic acid and on hepatic drug metabolizing enzyme activities in rats. Horibe, Y; Ito, Y; Iwaki, M; Ogiso, T; Yoneda, I, 1989)	0.28
" Dose-response effects for the induction of total cytochrome P450 ethoxyresorufin-O-deethylase (EROD) activity, and benzphetamine demethylase (BPDM) activity were studied using 10 selected tetra- to hexachlorinated PCB congeners."	( Effects of polychlorinated biphenyls on cytochrome P450 induction in the chick embryo hepatocyte culture. Robertson, LW; Rodman, LE; Shedlofsky, SI; Swim, AT, 1989)	0.28
" No dose-response curve was seen in animals which had only been pretreated with phenobarbital."	( Acute desensitization of pituitary FSH response to LHRH in ovariectomized rats: further evidence that in the presence of ovarian proteins the LHRH-dependent, LH-like component of FSH release becomes apparent. de Koning, J; Lambalk, CB; Schoemaker, J; van Dieten, JA; van Rees, GP, 1989)	0.5
"In order to evaluate the role played by polymorphism in the mechanical strength of solid dosage forms (e."	( Methodology for a better evaluation of the relation between mechanical strength of solids and polymorphic form. Beyer, C; Doelker, E; Graf, E; Kopp, S; Kubel, F, 1989)	0.28
" These results support the increased use of dosing aids for PHT that may help clinicians more accurately choose PHT doses and estimate time to steady state."	( Dosing accuracy of antiepileptic drug regimens as determined by serum concentrations in outpatient epilepsy clinic patients. Privitera, MD, 1989)	0.28
"The dose-response and plasma concentration-response relationships of cyclosporine after both inducing and inhibiting its metabolism were studied in a mouse heart transplant model."	( In vivo evaluation of the effects of altered cyclosporine metabolism on its immunosuppressive potency. Babany, G; Babany, I; Kates, RE; Morris, RE; Shepherd, S, 1989)	0.28
"In 43 ICU patients undergoing continuous volume constant hemofiltration (CVHF), the pharmacokinetics of 12 drugs were investigated to ensure correct dosage adjustments."	( [Dosage adjustment of drugs during continuous hemofiltration. Results and practical consequences of a prospective clinical study]. Dehne, M; el Abed, K; Hofmann, W; Kroh, U; Lennartz, H, 1989)	0.28
" The two drugs were administered four times a day in double dummy conditions, according to a fixed-flexible decreasing dosage schedule (six days basic regimen)."	( Double blind study on the efficacy and safety of tetrabamate and chlordiazepoxide in the treatment of the acute alcohol withdrawal syndrome. Chabot, F; Chawla, S; Forest, JC; Garcin, F; Guay, D; Huot, J; Marquis, PA; Martin, S; Radouco-Thomas, S; Stewart, G, 1989)	0.28
" Animals were dosed intraperitoneally (i."	( Effect of diet and route of administration on the DNA binding of aflatoxin B1 in the rat. Bjeldanes, LF; Salbe, AD, 1989)	0.28
" Dose-response curves for the behavioral and antiseizure effects of phenobarbital were similar."	( Effects of phenytoin and phenobarbital on schedule-controlled responding and seizure activity in the amygdala-kindled rat. Jakubow, J; Poling, A; Renfrey, G; Schlinger, H, 1989)	0.82
" In rats, repeated administration of either xylidine for 10 days failed to increase the appearance of metabolites, but 3-methylcholanthrene (3-MC) did increase the urinary concentration of AAMBA in 2,4-DMA dosed rats."	( The in vivo oxidative metabolism of 2,4- and 2,6-dimethylaniline in the dog and rat. Barker, SA; Hardy, ML; Short, CR, 1989)	0.28
" Our study demonstrates that current IV dosing of phenobarbital 20 mg/kg given intraosseously obtains and maintains therapeutic serum levels."	( Comparison of intraosseous and intravenous routes of anticonvulsant administration in a porcine model. Jaimovich, DG; Peters, GR; Ringer, TV; Shabino, CL, 1989)	0.53
"Studies were conducted to examine the temporal changes in phenobarbital pharmacokinetics during chronic dosing in dogs."	( Pharmacokinetics of phenobarbital in dogs given multiple doses. Pedersoli, WM; Ravis, WR; Wike, JS, 1989)	0.84
" Our findings thus indicate that in the study of drug actions on the EEG of anaesthetized animals, the results obtained not only represent the interaction of the anaesthetic and the drug on the animal EEG but is also a reflection of the dosage of the anaesthetic employed."	( EEG in anaesthetized rats. Chua, ME; Sim, MK, 1989)	0.28
" The metabolic disposition of antipyrine (AP) and m-xylene (XYL) has been studied in rats pretreated for a prolonged period with XYL, dosed alone or in combination with ethanol, phenobarbital (PB), or 3-methylcholanthrene (MC)."	( Metabolism of antipyrine and m-xylene in rats after prolonged pretreatment with xylene alone or xylene with ethanol, phenobarbital or 3-methylcholanthrene. Aitio, A; Elovaara, E; Engström, K; Hase, T; Häyri, L, 1989)	0.68
" The profiles of isoenzymes induced in vitro were compared with those induced in liver microsomes of rats dosed with the same agents."	( Induction of cytochrome P-450 in cultured rat hepatocytes. The heterogeneous localization of specific isoenzymes using immunocytochemistry. Bars, RG; Elcombe, CR; Mitchell, AM; Wolf, CR, 1989)	0.28
" The low dosage reduced total AD accrued during each kindling stage but failed to alter kindling rate."	( The NMDA-receptor antagonist, MK-801, suppresses limbic kindling and kindled seizures. Gilbert, ME, 1988)	0.27
" The dose-response relationship was also determined in juvenile rats for a single and for up to 64 daily doses of 3 mg/kg DENA started on day 32 of age."	( The effect of single versus split doses of diethylnitrosamine on the induction of gamma-glutamyltranspeptidase-foci in the livers of adult and juvenile rats. Herren-Freund, SL; Khoury, MM; Long, RE; Pereira, MA, 1986)	0.27
" Similar dose-response data were obtained at various doses of two promoting agents effective in hepatocarcinogenesis, PB and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in livers of F-344 female rats following initiation with DEN (10 mg/kg) 24 h post-70% hepatectomy."	( A method to quantitate the relative initiating and promoting potencies of hepatocarcinogenic agents in their dose-response relationships to altered hepatic foci. Campbell, HA; Glauert, HP; Goldsworthy, TL; Kennan, W; Maronpot, RR; Moran, S; Pitot, HC, 1987)	0.27
"Three-week dosing periods at one of six oral phenobarbital doses between 15 and 400 mg/day were used to achieve steady states for induction of plasma alpha 1-acid glycoprotein concentration (AGP) in beagle dogs."	( Dose-response behavior of the induction of alpha 1-acid glycoprotein by phenobarbital in the dog. Abramson, FP, )	0.62
" Since the normal human dosage of paracetamol is up to 4 g/day, which is equivalent to 1% of the diet, the possibility of induction of amino acid deficiency by chronic use of paracetamol in normal dosage is raised."	( Effect of D- or L-methionine and cysteine on the growth inhibitory effects of feeding 1% paracetamol to rats. Armstrong, GR; Beales, D; McLean, AE, 1989)	0.28
" Diethyldithiocarbamate (DDC), known to inhibit mixed-function oxidase activity, has no effect on survival rate when this compound is used in a dosage of 300 mg/kg 45 min before or 10 min after parathion intoxication."	( Parathion-provoked lethality in rats is reduced by diethyldithiocarbamate. Homann, J; Matthes, KJ; Schneider, S, 1985)	0.27
" In the case of diazepam, clonazepam, ethosuximide or trimethadione, the TE/TF ratio was decreased dose-dependently, but the slope of the dose-response regression line was less steep than that obtained by the administration of PB, PNT, CBZ, VPA or primidone."	( [The correlation between concentrations of anticonvulsive drugs in the brain and various parameters of maximal electroshock seizures in mice]. Kishita, C, 1986)	0.27
" The two cortical sites were distinguished by significantly different dose-response curve slopes for the suppression of afterdischarge duration by PHT, CBZ and VPA, which suggests more than one mechanism of action for these drugs."	( Differential antiepileptic sensitivity between cortical sites in the rat. Iragui, VJ; Kalichman, MW; Moss, KA, )	0.13
" Ethylmorphine N-demethylation was decreased after dosing with the imidazo[4,5-b]pyridine-containing drug."	( The induction profile of three orally active imidazopyridine-containing cardiotonic agents in rat hepatic microsomes. Bernstein, JR; Franklin, RB, 1986)	0.27
" Five animals per group were killed 2 days after dosing and another five animals were killed 7 days later for the determination of hepatic microsomal enzyme activities, histological changes and 14C-content in the major organs and tissues."	( Effect of phenobarbital and polychlorinated biphenyls on the toxicity and disposition of 1,2,4,5-tetrachlorobenzene in the rat. Chu, I; Valli, VE; Villeneuve, DC; Yagminas, A, 1986)	0.67
" Modifications of the usual dosage regimen in malnutrition are recommended."	( Pharmacokinetics of phenobarbitone in protein energy malnutrition. Raina, RK; Sharma, DB; Syed, GB, 1986)	0.27
" The time course and dose-response for the decrease in P-450 2c and its mRNA differed markedly from that for induction of P-450c, indicating that the effects of HCB on the two proteins may involve different mechanisms."	( Suppression of the constitutive, male-specific rat hepatic cytochrome P-450 2c and its mRNA by 3,4,5,3',4',5'-hexachlorobiphenyl and 3-methylcholanthrene. Goldstein, JA; Wadhera, A; Waxman, DJ; Yeowell, HN, 1987)	0.27
" We founded a good relationship between PRI dosage and PB plasma levels."	( [Usefulness of the evaluation of plasma levels of primidone and phenobarbital]. Franzoni, E; Govoni, M; Mambelli, M; Masoni, P, )	0.37
" In response to the effects of enzyme induction, valproate dosage may need to be doubled to maintain therapeutic serum levels."	( Pharmacologic interactions between valproate and other drugs. Bourgeois, BF, 1988)	0.27
" We conclude that compliance with the once-daily regimen was best, but that compliance with a twice-daily regimen was very similar, and both were superior to dosing three times a day."	( Use of a pharmacologic indicator to compare compliance with tablets prescribed to be taken once, twice, or three times daily. Birtwell, AJ; Feely, MP; Hay, A; Pullar, T; Wiles, PG, 1988)	0.27
"The dose-response of diethylnitrosamine (DENA) initiation of hepatocarcinogenesis was determined in infant Balb/c male mice with and without subsequent phenobarbital treatment."	( Dose-response relationship of diethylnitrosamine-initiated tumors in neonatal balb/c mice: effect of phenobarbital promotion. Klaunig, JE; Pereira, MA; Ruch, RJ; Weghorst, CM, 1988)	0.69
" The results of dissolution study indicated that agar beads could be useful for the preparation of sustained release dosage forms."	( Preparation and characterization of agar beads containing phenobarbitone sodium. el-Helw, Ael R; el-Said, Y, )	0.13
"Although phenobarbital is the most widely used drug to control seizures, dosage guidelines are not available for infants of varying gestational ages."	( Developmental aspects of phenobarbital dosage requirements in newborn infants with seizures. Edwards, RC; Masuoka, T; Nahata, MC, 1988)	1
" Therefore phenobarbitone does not have seem to have any significant effect on cerebral haemodynamics up to a dosage of 20 mg/kg, so that there is no apparent effect on the risk of cerebral haemorrhage."	( [Doppler flow velocities in cerebral arteries in relation to intravenous phenobarbital in premature infants weighing between 500 and 1,500 g]. Jorch, G; Michel, E; Rabe, H; Rickers, E; Stöhr, G; Süllwald, A, 1988)	0.51
"001), indicating that, if PB treatment is given without variations in dosage and if diuresis is not impaired, blood barbiturate level may be monitored through urine assays."	( [Monitoring of phenobarbital use during the neonatal period by means of urinalysis]. Cavo, L; Fabris, C; Licata, D; Tappi, E; Voglino, GF, )	0.48
"A technique for evaluating signs and symptoms of alcohol withdrawal that provides an accurate guide to benzodiazepine dosage is presented."	( Signs and symptoms assessment: a guide for the treatment of the alcohol withdrawal syndrome. Massman, JE; Tipton, DM, )	0.13
"0 mg/kg AOAA significantly potentiated the effects of diazepam, as indicated by a significant shift to the left in the diazepam dose-response curve relative to diazepam alone."	( Potentiation of the anticonflict effects of diazepam, but not pentobarbital and phenobarbital, by aminooxyacetic acid (AOAA). Beshears, JF; Commissaris, RL; Halas, NA; McCloskey, TC, 1988)	0.5
" Phenobarbital, at a dosage yielding serum barbiturate levels greater than those seen with primidone, was not better than placebo."	( Double-blind comparison of primidone and phenobarbital in essential tremor. Calzetti, S; Perucca, E; Sasso, E, 1988)	1.45
" Immunoblot analysis with monoclonal antibodies directed against cytochromes P-450b and P-450e indicate that HCB induces both isozymic species at the three dosage levels examined (10, 90, and 180 mg/kg)."	( Co-induction of cytochrome P-450 isozymes in rat liver by 2,4,5,2',4',5'-hexachlorobiphenyl or 3-methoxy-4-aminoazobenzene. Hantelle, P; Kelley, M; Levin, W; Safe, S; Thomas, PE, 1987)	0.27
" Thus, frequent phenytoin serum concentration determinations or a change in phenytoin dosing rate are probably not necessary after adding phenobarbital."	( Phenobarbital does not alter phenytoin steady-state serum concentration or pharmacokinetics. Browne, TR; Evans, BA; Evans, J; Greenblatt, DJ; Mikati, MA; Szabo, GK, 1988)	1.92
" Treatment with PB or CCl4 with the dosage and schedules employed proved to be effective in markedly modifying the N-demethylation of the three dimethyltriazenes tested, as had been determined in vitro."	( Effects of an inducer and an inhibitor of hepatic metabolism on the antitumor action of dimethyltriazenes. Giraldi, T; Lassiani, L; Perissin, L; Sava, G; Zorzet, S, 1988)	0.27
" The slopes of the dose-response curves and the order of potency of these metabolites differed significantly between rats and mice, suggesting that different mechanisms of single-strand break induction may be involved in the two species."	( Induction of strand breaks in DNA by trichloroethylene and metabolites in rat and mouse liver in vivo. Bull, RJ; Nelson, MA, 1988)	0.27
" A dose-response relation for cataractogenesis was evident in C57BL/6 mice using doses of 300 and 400 mg/kg, with the higher dose producing similar plasma acetaminophen concentrations but twofold higher glucuronide concentrations."	( Pharmacological studies on the in vivo cataractogenicity of acetaminophen in mice and rabbits. Avaria, M; Basu, PK; Lubek, BM; Wells, PG, 1988)	0.27
" At the end of this period, P was continued at the same dosage but F (300 mg daily) was added and both drugs were given simultaneously for a further eight-day period (period P + F)."	( Changes in plasma activities of lipolytic enzymes and lipids of normolipidemic subjects given phenobarbital, a strong microsomal inducer, alone or in combination with fenofibrate. Desager, JP; Harvengt, C; Heller, FR, 1988)	0.49
" Based on the results of the present study, an oral dosing regimen of 11 mg/kg of body weight every 24 h can be recommended."	( A pharmacokinetic study of phenobarbital in mature horses after oral dosing. Duran, SH; Pedersoli, WM; Ravis, WR; Schumacher, J, 1987)	0.57
"To study the effects of SKF-525A, an inhibitor of cytochrome P-450, and of sodium phenobarbital (PB), a drug-metabolizing enzyme inducer, on the teratogenicity of thiabendazole (TBZ), pregnant mice were given ip either a single dose of 40 mg SKF-525A/kg 1 hr before oral dosing with 250 or 500 mg TBZ/kg or a dose of 75 mg PB/kg/day on three consecutive days before oral administration of a dose of 500 or 1000 mg TBZ/kg."	( Effects of pretreatment with SKF-525A or sodium phenobarbital on thiabendazole-induced teratogenicity in ICR mice. Imamichi, T; Ogata, A; Sasaki, M; Suzuki, K; Yoneyama, M, 1987)	0.75
" Male Wistar rats, dosed daily with 50 mg AA/100 g body weight for 10 weeks, demonstrated a small non-significant increase in hepatic, pulmonary and colon cytochrome P-450 (Cyt."	( Effect of excessive intake of ascorbic acid on hepatic and extra-hepatic phase I and phase II drug metabolism in rat. Gupta, MP; Khanduja, KL; Koul, A; Koul, IB; Sharma, RR, 1987)	0.27
" A dose-response for induction by PB was observed in embryonic hepatic microsomes as early as 7 DI, whereas a low level of cytochrome P-450 was detected in control 7 DI microsomes using the reduced CO vs oxidized CO difference spectrum."	( Ontogeny of the chicken cytochrome P-450 enzyme system. Expression and development of responsiveness to phenobarbital induction. Bloom, SE; Lorr, NA, 1987)	0.49
" Input variables were weight, sex, height, age, concomitant drugs and diseases, phenobarbital dosage regimen, and the time and reported value of all SPC."	( Serum phenobarbital concentration predictions by a personal computer software system. Embil, AS; Gingery, JW; Jernigan, JA; Robinson, JD, 1987)	0.98
"The anticonvulsant effect of phenobarbital was examined in young (6 month old) and old (24 month old) BDF1 female mice consisting of three groups each (one control and two chronically dosed phenobarbital groups), using the abolition of the tonic hindlimb extensor component of maximal electroshock seizure as the index."	( The effect of age on the adaptation of the brain to the anticonvulsant effect of phenobarbital in mice. Kanai, S; Kitani, K; Masuda, Y; Nokubo, M; Ohta, M; Sato, Y, 1986)	0.79
" The tested medication has a favorable therapeutic spectrum as a result of the low dosage of the individual substances."	( [Bronchospasmolytic effectiveness of controlled drug combinations]. Forche, G; Harnoncourt, K; Zenker, G, 1986)	0.27
" The most common of these causes include malpractice of the dosage build-up in the absence of the clinical effect, polytherapy--not infrequently with drugs of the same chemical group, and insufficient attention to the potentiating drug interaction."	( [Phenomenon of "paradoxical poisoning" during antiepileptic therapy]. Geladze, TSh, 1986)	0.27
"The dose-response relationship was determined in rats for the enhancement by phenobarbital of diethylnitrosamine (DENA)-initiated neoplastic nodules and hepatocellular carcinomas."	( Dose-response relationship of phenobarbital promotion of diethylnitrosamine initiated tumors in rat liver. Herren-Freund, SL; Long, RE; Pereira, MA, 1986)	0.79
" Data were excluded for patients who required dosage adjustments because of toxicity or seizures."	( Effect of influenza vaccine on serum anticonvulsant concentrations. Fidone, GS; Jann, MW, 1986)	0.27
" In subchronic studies, PB was administered in drinking water to 5-week-old male hamsters for periods of 8 or 16 weeks at dosage levels of 250, 500, or 1000 ppm."	( Lack of effect of phenobarbital on hepatocellular carcinogenesis initiated by N-nitrosodiethylamine or methylazoxymethanol acetate in male Syrian golden hamsters. Anderson, LM; Diwan, BA; Hagiwara, A; Rice, JM; Ward, JM, 1986)	0.6
" Qualitative and quantitative differences in pharmacokinetics and pharmacodynamics of drugs should be considered before dosage regimens can be established."	( [Peculiarities of drug therapy in childhood]. Kusenbach, G; Reinhardt, D, 1986)	0.27
" The dosing of various drugs currently in use is also discussed."	( The neonatal narcotic abstinence syndrome: a brief review. Calabrese, JR; Gulledge, AD, 1985)	0.27
"Water-soluble aflatoxin conjugates prepared from urine samples from rats, mice and rhesus monkeys dosed with [14C]aflatoxin B1 (AFB1) ip or iv were hydrolysed by enzymes (beta-glucuronidase and sulphatase), acid or a combination of both treatments."	( Characterization of water-soluble glucuronide and sulphate conjugates of aflatoxin B1. 1. Urinary excretion in monkey, rat and mouse. Hsieh, DP; Marshall, MR; Wei, CI, 1985)	0.27
" Acute intraperitoneal administration of the other drugs revealed VPA to be an effective anticonvulsant agent, whereas ethosuximide and diazepam were ineffective at dosage levels that are normally effective in mice as determined by classical testing methods such as electroshock and chemoshock."	( Seizure control following administration of anticonvulsant drugs in the quaking mouse. Abbott, LC; Bennett, GD; Finnell, RH; Taylor, SM, 1985)	0.27
" No changes in pharmacokinetics were seen with repeated dosing in mice or with administration of the protective agent phenyl AIC."	( CB 1954 revisited. I. Disposition kinetics and metabolism. Talbot, K; White, RA; Workman, P, 1986)	0.27
"Fifty-nine patients with chronic generalized tonic-clonic or partial seizures refractory to the maximally tolerated daily dosage of single-drug therapy with carbamazepine, phenytoin, phenobarbital, or primidone subsequently received single-drug therapy with another one of these primary anticonvulsant drugs."	( Alternative single anticonvulsant drug therapy for refractory epilepsy. Richter, K; Schmidt, D, 1986)	0.46
" In the antibiotic-pretreated rats dosed with m-DCB, metabolite concentrations in the blood and the three tissues markedly decreased."	( Evidence that methylsulfonyl metabolites of m-dichlorobenzene are causative substances of induction of hepatic microsomal drug-metabolizing enzymes by the parent compound in rats. Kato, Y; Kimura, R; Kogure, T; Murata, T; Sato, M, 1986)	0.27
" A simple two-stage model of rat hepatocarcinogenesis with a single ip dose of diethylnitrosamine (DEN) as the initiator and sodium phenobarbitone or ethanol given in the drinking-water for 12-18 months as the promoter was used to investigate dose-response relationships for initiation and promotion."	( Dose-response relationships for initiation of rat liver tumours by diethylnitrosamine and promotion by phenobarbitone or alcohol. Driver, HE; McLean, AE, 1986)	0.27
" Plasma 3MI was still detectable 12 and 36 hours after dosing in phenobarbital-treated and control ponies, respectively."	( Effects of phenobarbital treatment on 3-methylindole toxicosis in ponies. Thomas, DE; Turk, MA, 1986)	0.9
" Therefore, it is not necessary to adjust PB dosage for time-dependent or dose-dependent changes in clearance during monotherapy."	( Studies with stable isotopes II: Phenobarbital pharmacokinetics during monotherapy. Browne, TR; Evans, BA; Evans, JE; Greenblatt, DJ; Szabo, GK, )	0.41
" The activities of NADPH-cytochrome P-450 reductase, AHH, and ECOD following treatment with HCB were similar to those found after dosing with PB."	( A comparison of the effects of hexachlorobenzene, beta-naphthoflavone, and phenobarbital on cytochrome P-450 and mixed-function oxidases in Japanese quail. Buhler, DR; Carpenter, HM; Williams, DE, 1985)	0.5
" This two-fold effect of rifampin offers an explanation for the discrepancy surrounding the dosage and species differences in hepatic induction reported in the literature."	( Effects of rifampin pretreatment on hepatic parameters in the rabbit. Iverson, F; Whitehouse, LW; Wong, LT, )	0.13
" Among Chinese epileptic patients, the saturation of phenytoin metabolism occurs at the dosage of 4 mg/kg/day."	( Steady-state serum levels of anticonvulsant drugs in Chinese epileptic patients living in Taiwan. Lai, ML, 1985)	0.27
" The dosage determination in the dialysis patients receiving these drugs is discussed."	( Effect of peritoneal dialysis on serum concentrations of three drugs commonly used in pediatric patients. Chow-Tung, E; John, EG; Lau, AH; Vidyasagar, D, 1985)	0.27
"The disposition of theophylline was examined in seven children with asthma on two occasions before and on one occasion after chronic phenobarbital dosing (2 mg/kg/day)."	( The effect of phenobarbital on theophylline disposition in children with asthma. Danish, M; Greene, J; Mansmann, HC; Ragni, MC; Rocci, ML; Saccar, CL; Yaffe, SJ, 1985)	0.83
" Both drugs were dosed according to the clinical requirement; the daily doses ranged from 5-17 mg/kg phenobarbital and from 17-70 mg/kg primidone."	( Therapeutic efficacy of phenobarbital and primidone in canine epilepsy: a comparison. Frey, HH; Löscher, W; Schwartz-Porsche, D, 1985)	0.79
" A direct dose-response relationship in induction of thyroid tumors was found in both male and female rats."	( Sex differential and dose dependence of phenobarbital-promoting activity in N-bis(2-hydroxypropyl)nitrosamine-initiated thyroid tumorigenesis in rats. Hiasa, Y; Kitahori, Y; Konishi, N; Lin, JC; Shimoyama, T, 1985)	0.54
" Differences in dose-response curves for certain mutagens using liver and intestinal microsomes are discussed in relation to variation in metabolism of promutagens."	( Characterization of a microsomal fraction from rat small intestine for metabolic activation of some promutagens. Combes, RD; Walters, JM, 1985)	0.27
" Dose-response induction of mice hepatic microsomal cytochrome P-450, aldrin epoxidase and dimethylaminoantipyrine N-demethylase gave ED50 values for TCPOBOP and five homologs."	( 1,4-Bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) and related compounds as inducers of hepatic monooxygenases. Structure-activity effects. Kelley, M; Lambert, I; Merrill, J; Safe, S, 1985)	0.27
"-1 the lower end of the teratogenic dose-response curve was determined for each drug."	( Fetal anticonvulsant syndrome in rats: effects on postnatal behavior and brain amino acid content. Vorhees, CV, )	0.13
" This has been applied to the analysis of some of these drugs in plasma taken from patients after therapeutic dosage and over-dosage."	( A rapid micro-method for the screening and measurement of barbiturates and related compounds in plasma by gas-liquid chromatography. Flanagan, RJ; Withers, G, 1972)	0.25
" The dosage of the hormone, the time of the neonatal period, and differences in the animal strain, are considered influencing factors on this effect."	( Some aspects of the mechanisms involved in steroid-induced sterility. Arai, Y, 1972)	0.25
" Hypocalcaemia was related to high dosage of anticonvulsant drugs, to multiple drug therapy, and to the use of individual anticonvulsant drugs in the following order, with decreasing order of importance: pheneturide, primidone, phenytoin, phenobarbitone."	( Disturbance of calcium metabolism by anticonvulsant drugs. Richens, A; Rowe, DJ, 1970)	0.25
"Administration of phenobarbital to rats in a dosage schedule previously demonstrated to increase hepatocellular binding of thyroxine results in increased hormonal turnover, due both to increased deiodination and to fecal disposition of thyroxine iodine."	( Increased thyroxine turnover and thyroidal function after stimulation of hepatocellular binding of thyroxine by phenobarbital. Bernstein, G; Oppenheimer, JH; Surks, MI, 1968)	0.79
" Where pA2 values (-log dose antagonist evoking a twofold shift for the agonist dose-response curve) could be calculated, no significantly different pA2 values against either agonist resulted."	( Calcium influx-dependent and -independent alpha 1-adrenoceptor-mediated processes of vasoconstriction in vivo do not operate via different alpha 1-adrenoceptor subtypes. de Jonge, A; Korstanje, C; Thoolen, MJ; Timmermans, PB; van Zwieten, PA; Wilffert, B, )	0.13
" We found a noticeable relationship between conduction velocity slowing and daily dosage for CBZ only."	( Anticonvulsant therapy and its possible consequences on peripheral nervous system: a neurographic study. Faedda, MT; Geraldini, C; Sideri, G, 1984)	0.27
" Ro 15-1788 antagonized the depressant effect of diazepam and shifted the dose-response curve of diazepam to the right in a parallel manner but could not reverse the depression produced by either phenobarbital or chlorpromazine."	( An imidazodiazepine derivative, Ro 15-1788, behaves as a weak partial agonist in the crossed extensor reflex. Kawasaki, K; Kodama, M; Matsushita, A, 1984)	0.46
" Following discrimination training subjects were tested for generalization to five dosage levels (5, 10, 15, 20, 25 mg/kg) of phenobarbital."	( Assessment of drug state dimensionality via drug-drug training and stimulus generalization testing. Akins, FR; Gouvier, WD; Trapold, MA, 1984)	0.47
" Dose-response data were obtained for barbiturate concentrations ranging from 1 microM to 3 mM."	( Effects of barbiturates on inhibitory and excitatory responses to applied neurotransmitters in Aplysia. Cote, IL; Wilson, WA, 1980)	0.26
" At the moment, xanthines are the drugs of choice, since they are both effective and safe, provided dosage is adjusted to each patient."	( [Drug treatment of apnoea in premature infants (author's transl)]. Klethi, J; Mack, G; Messer, J; Willard, D, 1981)	0.26
" An alteration in the dosage schedule is usually only necessary for drugs with a small therapeutic ratio."	( Clinical implications of enzyme induction and enzyme inhibition. Breckenridge, AM; Park, BK, )	0.13
" The 3-methylcholanthrene-dependent increases in 2- and 3-hydroxylation appear due to induction of a single form of cytochrome P-450, as indicated by similar dose-response relationships and similar changes in sensitivity to the inhibitors."	( Biphenyl metabolism by rat liver microsomes: regioselective effects of inducers, inhibitors, and solvents. Haugen, DA, )	0.13
" In support of this hypothesis, both cytochrome P-450 concentrations and the rate of catalysis of the D-homoannulation pathway by this enzyme were significantly decreased in hepatic microsomes from rhesus monkeys which had been administered mestranol and/or ethynerone (17 alpha-ethynylated steroids) at dosage levels mimicking human exposure to oral contraceptive agents."	( Cytochrome P-450-dependent oxidation of the 17 alpha-ethynyl group of synthetic steroids. D-homoannulation or enzyme inactivation. Au, WY; Hill, DE; Kadlubar, FF; Schmid, SE; Slikker, W, )	0.13
" The reduction in steady-state beta-adrenergic receptor drug concentration following enzyme induction is sufficiently large that an altered pharmacodynamic response would be expected if no dosage modification is made."	( Enzyme induction and beta-adrenergic receptor blocking drugs. Branch, RA; Herman, RJ, 1984)	0.27
" In the first experiment, the lower end of the malformation dose-response curves for diphenylhydantoin (DPH), trimethadione (TMD) and phenobarbital (PB) were established."	( Fetal anticonvulsant syndrome in rats: dose- and period-response relationships of prenatal diphenylhydantoin, trimethadione and phenobarbital exposure on the structural and functional development of the offspring. Vorhees, CV, 1983)	0.67
" The results show that all three of these anticonvulsants depress postjunctional sensitivity to released acetylcholine producing parallel dose-response curves for MEPP amplitude inhibition."	( Differential effects of the anticonvulsants phenobarbital, ethosuximide and carbamazepine on neuromuscular transmission. Alderdice, MT; Trommer, BA, 1980)	0.52
" Advice about the dosage regimen in such cases is given."	( Pharmacokinetic aspects of guanfacine withdrawal syndrome in a hypertensive patient with chronic renal failure. Comoy, E; Fillastre, JP; Godin, M; Guerret, M; Kiechel, JR; Lavene, D, 1983)	0.27
" In addition to the structure-activity correlations noted for PCBs, the 2,2',3,4,4',5-hexachlorobiphenyl congener also elicited a dose-response induction of two PB-inducible enzymes, aldrin epoxidase and dimethylaminoantipyrine N-demethylase."	( Polychlorinated biphenyls as phenobarbitone-type inducers of microsomal enzymes. Structure-activity relationships for a series of 2,4-dichloro-substituted congeners. Bandiera, S; Copp, L; Denomme, MA; Lambert, I; Safe, L; Safe, S, 1983)	0.27
" Phenobarbital-induced embryos had an increased UDS response while TCB-induced embryos had a decreased UDS response, relative to noninduced embryos, for each dosage of AFB1."	( Correlation between mixed-function oxidase enzyme induction and aflatoxin B1-induced unscheduled DNA synthesis in the chick embryo, in vivo. Bloom, SE; Hamilton, JW, 1984)	1.18
" Dose-response curves in benzene-treated mice were much steeper with 3-MCA induction than without."	( Modifications in the myeloclastogenic effect of benzene in mice with toluene, phenobarbital, 3-methylcholanthrene, Aroclor 1254 and SKF-525A. Gad-El-Karim, MM; Harper, BL; Legator, MS, 1984)	0.5
" They were subsequently followed up as outpatients, and Phenobarbital and sodium valproate levels were measured regularly to ascertain compliance with the treatment and to adjust the dosage accordingly."	( Prevention of recurrent febrile convulsions--a randomized therapeutic assay: sodium valproate, phenobarbital and placebo. Gilly, R; Mamelle, JC; Mamelle, N; Plasse, JC; Revol, M, 1984)	0.73
" Dose-response curves for subcutaneous (SC) morphine (0."	( Reinforcing properties of morphine and naloxone revealed by conditioned place preferences: a procedural examination. Iversen, SD; Mucha, RF, 1984)	0.27
" Conversely, anticonvulsants may influence the dosage requirements of oral anticoagulants by inducing their metabolism."	( Interactions between anticonvulsants and other commonly prescribed drugs. Kutt, H, 1984)	0.27
" Multiple metabolic pathways, including dehydrogenation, isomerization, hydration, hydroxylation, reduction and epoxidation were inferred from the metabolites obtained after dosage of the unsaturated metabolites."	( Aspects of the metabolism of valproic acid. Granneman, GR; Kesterson, JW; Machinist, JM; Wang, SI, 1984)	0.27
" Significant positive correlations were found between the dosage of CBZ, DPH, PMD and PB and both indices of enzyme induction."	( A comparative study of the relative enzyme inducing properties of anticonvulsant drugs in epileptic patients. Hedges, A; Makki, KA; Perucca, E; Richens, A; Ruprah, M; Wilson, JF, 1984)	0.27
" The drug did, however, induce hepatic lipid accumulation in mature rats and in young rats dosed concomitantly with phenobarbital."	( The hepatotoxicity of valproic acid and its metabolites in rats. I. Toxicologic, biochemical and histopathologic studies. Granneman, GR; Kesterson, JW; Machinist, JM, )	0.34
" Depletion of serotonin with p-chlorophenylalanine, p-chloroamphetamine and 5,7-dihydroxytryptamine did not affect the initial dose-response curve to the centrally injected barbiturate, but all treatments resulted in significant delays in tolerance development."	( The role of cerebral serotonin in the development of tolerance to centrally administered phenobarbital. Lyness, WH; Mycek, MJ, 1980)	0.48
" Fluctuations in the blood phenobarbital content from one administration to another is important for selecting its optimal dosage and the interval between intakes."	( [Concentration of phenobarbital in biological fluids during the treatment of epilepsy patients]. Antadze, ZI; Okudzhava, VM; Vetrogon, FG, 1984)	0.9
" The procedure presented here provides possibilities for the assay of these compounds in various dosage forms."	( [Gas chromatography determination of atropine, theophylline, phenobarbital and aminophenazone in tablets]. Majlát, P, 1984)	0.51
"A reverse-phase high-performance liquid chromatographic method for the quantitation of phenobarbital and phenobarbital sodium in pharmaceutical dosage forms (elixir, injection, and tablets) was developed."	( Quantitation of phenobarbital and phenobarbital sodium in pharmaceutical dosage forms. Das Gupta, V, 1984)	0.84
") at 4 weeks of age with N-nitrosodiethylamine (DEN) at a dosage of 80 mg/kg."	( Di(2-ethylhexyl)phthalate but not phenobarbital promotes N-nitrosodiethylamine-initiated hepatocellular proliferative lesions after short-term exposure in male B6C3F1 mice. Lynch, P; Ohshima, M; Riggs, C; Ward, JM, 1984)	0.55
" Serum concentrations of phenobarbital were measured in all dogs before and after primidone therapy was initiated, to ensure that the primidone dosage achieved comparable or higher values when derived from primidone."	( Efficacy of primidone in dogs with seizures unresponsive to phenobarbital. Farnbach, GC, 1984)	0.81
" Five groups received the prototype mixed-function oxidase (MFO) enzyme inducer phenobarbital (PB) at a dosage of 50 mg/kg body weight for 3 consecutive days by intraperitoneal (i."	( The effect of hepatic mixed-function oxidase enzyme inducers on the development of tri-o-tolyl phosphate-induced delayed neurotoxicity. Bursian, SJ; Calabrese, LF, 1984)	0.49
" Fifty-one percent of the 53 patients receiving phenytoin were completely controlled at either below or above the 10 to 20 micrograms/ml range, suggesting that individual dosage adjustment is preferably based on clinical judgment rather than numerical limits of published therapeutic ranges."	( Therapeutic plasma levels of phenytoin, phenobarbital, and carbamazepine: individual variation in relation to seizure frequency and type. Haenel, F; Schmidt, D, 1984)	0.54
"Application software for economical and convenient calculation of median effective doses, confidence limits, potency ratios and slopes of quantal dose-response curves using a microcomputer is presented."	( A probit analysis program for the personal computer. Schoofs, GM; Willhite, CC, 1984)	0.27
" After an initial 2 week dosing period, all individuals additionally received 600 mg rifampicin daily for 3 weeks followed by a 4 week period during which again only the propranolol was given."	( Induction of propranolol metabolism by rifampicin. Herman, RJ; Nakamura, K; Wilkinson, GR; Wood, AJ, 1983)	0.27
" One-half the rats were sacrificed at the end of the dosing period and the other half were killed 4 weeks later."	( NADPH-diaphorase used to estimate alterations in the toxic rapeseed oil syndrome. Repetto, M; Sanz, P; Villar, P, 1983)	0.27
" Chloramphenicol was administered by the intravenous, intramuscular or oral route and dosage ranged between 12 and 210 mg/kg/day."	( The pharmacokinetics of chloramphenicol in the neonate and young infant. de Louvois, J; Hurley, R; Mulhall, A, 1983)	0.27
" d-Amphetamine, cocaine, and caffeine each had the effect of elevating both bite and lever press responses; nicotine, chlorpromazine, chlordiazepoxide, and diazepam each elevated lever press responding while depressing bite responding across a portion of the dosage range; phenobarbital, alcohol, and morphine had the effect of depressing both bite and lever press responses but lever pressing was selectively more depressed than biting."	( Unique influences of ten drugs upon post-shock biting attack and pre-shock manual responding. Emley, GS; Hutchinson, RR, 1983)	0.44
" Persons taking these drug combinations were identified and matched on the basis of age, sex, body weight, and antiepileptic drug (AED) dosage with persons from the same population who were taking only the AEDs."	( Interaction between phenobarbital and thioridazine. Gay, PE; Madsen, JA, 1983)	0.59
"A rat model of phenobarbital tolerance and physical dependence has been developed based on the 'maximally tolerable, chronically equivalent' dosing paradigm."	( Phenobarbital tolerance and physical dependence: chronically equivalent dosing model. Boisse, NR; Gay, MH; Guarino, JJ; Ryan, GP, 1983)	2.06
" One subject who was administered dextroamphetamine did not produce a wave consistent with amphetamine with a dosage of 5 mg."	( Qualitative measurement of drugs. Gilbert, LM; Golz, A; Komorowski, FS; Westerman, ST, 1984)	0.27
"phenobarbital dosing requirements and plasma clearance were examined for asphyxiated and nonasphyxiated neonates."	( The influence of asphyxia on phenobarbital dosing requirements in neonates. Boer, HR; Erkan, NV; Gal, P; Toback, J, 1984)	2
" These LAAM-induced changes demonstrated dose- and time-dependence within that dosage range producing mortality."	( L-alpha-acetylmethadol-induced tissue alterations in mice. Freeman, RW; Harbison, RD; James, RC, 1984)	0.27
" Further, for dogs given phenobarbital, there was a sixfold variation between dosage and achieved serum concentration, whereas dogs given primidone manifested even greater variability between dosage and serum concentration."	( Serum concentrations and efficacy of phenytoin, phenobarbital, and primidone in canine epilepsy. Farnbach, GC, 1984)	0.83
" Plasma phenobarbital concentrations achieved with the five dosage forms differed by less than 20% within 2-3 h after dosing."	( Absorption of phenobarbital from tablets and elixir. Meyer, MC; Raghow, G; Rotenberg, KS; Schary, WL; Straughn, AB, 1984)	1.06
" After the first week of life, drug eliminating mechanisms mature and drug dosage requirements often increase dramatically."	( Antiepileptic drug utilization in pediatric patients. Dodson, WE, 1984)	0.27
" At dosage levels of 30 and 150 mumol ."	( Polychlorinated biphenyl isomers and congeners as inducers of both 3-methylcholanthrene- and phenobarbitone-type microsomal enzyme activity. Cockerline, R; Parkinson, A; Safe, S, 1980)	0.26
"A number of highly purified polychlorinated biphenyl (PCB) isomers and congeners were synthesized and administered to male Wistar rats at dosage levels of 30 and 150 mumol ."	( Polychlorinated biphenyls as inducers of hepatic microsomal enzymes: structure-activity rules. Parkinson, A; Robertson, L; Safe, L; Safe, S, 1980)	0.26
" The dosage was phenobarbitone 3-6 mg/kg per day; sodium valproate 30-60 mg/kg per day."	( Continuous sodium valproate or phenobarbitone in the prevention of 'simple' febrile convulsions. Comparison by a double-blind trial. Bower, B; Ngwane, E, 1980)	0.26
" On the basis of results obtained with three tablet preparations, they have found that CUT specification may favourably be used, applying appropriate methods of determination, in the case of dosage forms for the better fulfilment of quality requirements."	( Application of content uniformity test to tablet preparations. Darbai, MJ; Hadady, KK; Kovács, I, 1980)	0.26
" The results also show that a low dosage has a favourable effect."	( Phenobarbital prophylaxis of post traumatic epilepsy. Bonuccelli, U; Del Tacca, M; Lenzi, B; Murri, L; Parenti, G, 1980)	1.7
" The beneficial effect of MET-TS therapy reported in a previous study (AFB2 dosage of 4 mg/kg) was not observed with the 3 mg/kg lethal dose."	( Effect of some enzyme inducers, fluids, and methionine-thiosulfate on induced acute aflatoxicosis in goats. Clark, JD; Hatch, RC; Jain, AV; Mahaffey, EA; Weiss, R, 1982)	0.26
" Fortunately, the drugs used by the majority of these patients are readily measured in plasma, and in most cases the plasma concentration is a valid measure of the appropriateness of the dosage of drug administered."	( Antiepileptic therapeutic drug monitoring. Cohan, SL, 1981)	0.26
" Animals were grouped in pairs for one of four treatments: 1) control, 2) oral dosing with sodium phenobarbital for 5 days, 3) dosing with sodium phenobarbital followed by oral dosing with aflatoxin B1, and 4) oral dosing with aflatoxin B1 for 5 days."	( Some effects of phenobarbital dosing of dairy cattle on aflatoxin M1 and fat in milk. Barnhart, HM; McGrew, PB; Mertens, DR; Wyatt, RD, 1982)	0.83
"The authors studied antipyrine disposition before and after delivery in 4 epileptic women whose anticonvulsant plasma level per dosage ratio was lowered during pregnancy, and compared the results to those found in nonpregnant women undergoing antiepileptic treatment (N = 6) and healthy women (N = 6)."	( Antipyrine disposition in relation to lowered anticonvulsant plasma level during pregnancy. Chiba, K; Ishizaki, T; Nakazawa, Y; Tabuchi, T; Wagatsuma, T, 1982)	0.26
" However, displacement alone, unlike induced metabolism, should not affect the drug's dose-response relationship."	( Drug interactions with valproic acid. Koch, KM; Levy, RH, 1982)	0.26
" Phenobarbital use should be monitored with serum drug levels and modification of recommended dosage regimens considered."	( Opiate v CNS depressant therapy in neonatal drug abstinence syndrome. Doberczak, TM; Kandall, SR; Korts, DC; Mauer, KR; Strashun, RH, 1983)	1.18
" These results suggest that the concentration of phenobarbital in the plasma, which is commonly used as a basis for adjusting phenobarbital dosage during pregnancy, is not an appropriate indicator of the dynamics of the drug."	( Pregnancy increases reactivity of mice to phenobarbital. Boggan, WO; Middaugh, LD; Zemp, JW, 1983)	0.78
" During this time it was necessary to administer theophylline at a dosage four times above that usually recommended."	( Effect of secobarbital on theophylline clearance. Blumer, NA; Maddox, RR; Paladino, JA, 1983)	0.27
" Maintenance period blood samples were taken from fasted dogs 7 hours after dosing in the 3rd, 5th, 7th, and 9th months of the trial to determine therapeutic serum concentrations of primidone and its metabolites."	( Therapeutic serum concentrations of primidone and its metabolites, phenobarbital and phenylethylmalonamide in epileptic dogs. Cunningham, JG; Haidukewych, D; Jensen, HA, 1983)	0.5
" Patients receiving anticonvulsant medication must make no change in drug dosage without medical guidance because of the risk of this catastrophic consequence."	( Anticonvulsants and neurogenic pulmonary edema. Mandel, S; Paschall, R, 1983)	0.27
" On the third day of therapy, trough concentration was determined; elimination rate constants were calculated using the two concentrations and the total dosage administered."	( Individualizing phenobarbital dosing in neonates. Erkan, NV; Gal, P; Gilman, ME; Toback, JW, )	0.48
" The radiation dosage in each group was equal to 1702 ret."	( The Cambridge glioma trial of misonidazole and radiation therapy with associated pharmacokinetic studies. Bleehen, NM, 1980)	0.26
" Ten of the studies are dose-response evaluations."	( Sleep spindles: pharmacological effects in humans. Hirshkowitz, M; Karacan, I; Thornby, JI, 1982)	0.26
"0% at discharge) versus polytherapy; degree of correspondence between recommended and observed dosage regimens (undertreatment being a more common problem than excessive dosing); and reporting of side effects."	( Quality of care of epilepsy in Italy: multi-hospital survey of diagnosis and treatment of 1104 epileptic patients. Beghi, E; Sasanelli, F; Spagnoli, A; Tognoni, G, 1982)	0.26
" The rats were then given a calculated LD50 dosage (13."	( Toxicologic study of carboxyatractyloside (active principle in cocklebur--Xanthium strumarium) in rats treated with enzyme inducers and inhibitors and glutathione precursor and depletor. Clark, JD; Hatch, RC; Jain, AV; Weiss, R, 1982)	0.26
"A method suitable for pulse dosing studies is described for the quantitation by gas chromatography mass spectrometry of phenobarbital (5-ethyl-5-phenylbarbituric acid), p-hydroxyphenobarbital (5-ethyl-5(4-hydroxyphenyl)barbituric acid) and, simultaneously, their (13C15N2)-labeled analogs in serum and urine."	( Simultaneous determination of phenobarbital and p-hydroxyphenobarbital and their stable isotope labeled analogs by gas chromatography mass spectrometry. Biemann, K; Biller, JE; Browne, TR; Van Langenhove, A, 1982)	0.76
" The high recovery of tertiary amine N-oxides in human urine after tiaramide dosing reflects the high activity of N-oxidation of tiaramide by human liver microsomes."	( Metabolism of tiaramide in vitro. I. Oxidative metabolism of tiaramide by human and rat liver microsomes. Iwasaki, K; Kamataki, T; Kato, R; Noguchi, H, 1982)	0.26
" Caffeine can shift the dose-response curve of chlorpromazine-inhibited sperm motility to right."	( Effects of chlorpromazine and other drugs acting on the central nervous system on human sperm motility. Chaput de Saintonge, DM; Hong, CY; Turner, P, 1982)	0.26
"High-performance liquid chromatographic separations are described for the analysis of hyoscyamine-atropine and scopolamine in combination pharmaceutical dosage forms containing phenobarbital."	( Belladonna alkaloids and phenobarbital combination pharmaceuticals analysis I: High-performance liquid chromatographic determinations of hyoscyamine-atropine and scopolamine. Pennington, LJ; Schmidt, WF, 1982)	0.76
"A high-performance liquid chromatographic separation is described for the analysis of phenobarbital in combination pharmaceutical dosage forms containing belladonna alkaloids."	( Belladonna alkaloids and phenobarbital combination pharmaceuticals analysis II: High-performance liquid chromatographic determination of phenobarbital. Pennington, LJ; Schmidt, WF, 1982)	0.79
"In order to find the optimal dosage schedule of phenobarbitone for neonatal convulsions, four groups of patients were studied."	( Phenobarbitone dosage in neonatal convulsions. Goldsmith, R; Ouvrier, RA, 1982)	0.26
" These recommendations provide initial maintenance dosage guidelines, which should be adjusted according to plasma concentrations and clinical effects."	( Phenobarbital maintenance dose requirements in treating neonatal seizures. Fischer, JH; Kriel, R; Lockman, LA; Zaske, D, 1981)	1.71
" The blood and brain concentrations of PhB during the dosing period were reduced abruptly on the 3rd or 4th day, corresponding well with the time course changes in the development of tolerance shown by rotarod performance."	( Tolerance to and dependence on barbiturates in mice reference to the data in rats. Hiramori, T; Tagashira, E; Urano, T; Yanaura, S; Yasukouchi, K, 1981)	0.26
"Healthy dogs were treated once a day for 26 days with a liquid, oral dosage form of digoxin (0."	( Serum digoxin concentrations in dogs before, during, and after concomitant treatment with phenobarbital. Ganjam, VK; Nachreiner, RF; Pedersoli, WM, 1980)	0.48
" Serum primidone concentrations decreased after repeated dosing and were measurable in only 1 dog 24 hours after the 21st dose and peak concentrations of 4 to 7 micrograms/ml were measured at 4 hours after the 22nd dose."	( Serum concentrations of primidone and its metabolites, phenylethylmalonamide and phenobarbital, in the dog. Yeary, RA, 1980)	0.49
" When the same tests were repeated in rats that had previously received an intracerebroventricular injection of 5,7-dihydroxyptamine (5,7-DHT) the dose-response curves for the pausing induced by all three hallucinogens were shifted to the left, while the behavioral disruption produced by phenobarbital was unaltered."	( Central 5-hydroxytryptamine and the effects of hallucinogens and phenobarbital on operant responding in rats. Commissaris, RL; Lyness, WH; Moore, KE; Rech, RH, 1981)	0.68
" This extremely high dosage of VC warranted the appearance of drastic symptoms of liver injury in the course of 20 h postexposure."	( Protective effect of methionine against vinyl chloride-mediated depression of non-protein sulphydryls and cytochrome p-450. Bogdanikowa, B; Dajniak, A; Klimczak, J; Sokal, JA; Wisniewska-Knypl, JM, 1981)	0.26
" Similar effects were observed with chronic dosing of cimetidine."	( Cimetidine: a specific inhibitor of hepatic aryl hydrocarbon hydroxylase (AHH) in the rat. Drew, R; Grygiel, JJ; Rowell, J, 1981)	0.26
" The time course and dose-response relationship of the induction brought about by trans-stilbene oxide were determined."	( Effect of inducers of drug-metabolizing enzymes on glutathione reductase and glutathione peroxidase in rat liver. Carlberg, I; Depierre, JW; Mannervik, B, 1981)	0.26
" In the case of clinial manifestation of side effects it might be concluded that the dosage of DPH should be reduced."	( Antiepileptic drug levels and side effects in man. Oettinger, B; Richter, K, 1980)	0.26
" Saliva samples were easily obtained and the measured concentrations were a valuable guide to drug dosage during the treatment period."	( Monitoring of phenobarbitone and phenytoin therapy in small children by salivary samples. Bacon, CJ; Hierons, AM; Mucklow, JC; Rawlins, MD; Webb, JK, 1981)	0.26
"The effects of long term, low dosage anticonvulsant drug therapy on the vitamin D and folacin status of young children was studied."	( Folic acid and vitamin D status of young children receiving minimal anticonvulsant drug therapy. Bailey, LB; Enneking-Ivey, O; Gawley, L; Hananian, J; Hurd, R, 1981)	0.26
" MMI and ETU were dosed simultaneously, one hour after dosing with SKF."	( Effects of pretreatment with SKF-525A, N-Methyl-2-thioimidazole, sodium phenobarbital, or methyl cholanthrene on ethylenethiourea-induced teratogenicity in rats. Iverson, F; Khera, KS, 1981)	0.5
" The mean dosage of barbexaclone was lower in patients who improved than in those who remained unchanged."	( [Barbexaclone in the treatment of the epilepsies (author's transl)]. Calzetti, S; Mancia, D; Visintini, D, )	0.13
"2) between both dosage forms."	( Pharmacokinetics and relative bioavailability of intramuscular phenobarbital sodium or acid in infants. Chiba, K; Ishizaki, T; Minagawa, K; Miura, H, 1981)	0.5
"Recent developments of clinical pharmacology show that in particular circumstances the determination of the plasmatic levels of drugs seems to be the best way to insure the best dosage schedules for each patient."	( Clinical pharmacokinetics: the pharmacological monitoring of plasmatic levels in therapy. Bonora, MR; Guaglio, R; Rondanelli, R; Terzoni, PA, 1980)	0.26
" In order to test the validity of FEAD as an absence seizure model, the present experiments determined dose-response relationships for the suppression of FEAD by six antiepileptic drugs with established clinical profiles."	( Flash-evoked afterdischarge in rat as a model of the absence seizure: dose-response studies with therapeutic drugs. Burnham, WM; King, GA; Livingston, KE, 1980)	0.26
" Twelve hours later and then every 24 hours until the fever had subsided the dosage was 5 mg/kg orally or intramuscularly."	( [Phenobarbital in febrile convulsions of children (author's transl)]. Lagenstein, I; Sternowsky, HJ, 1981)	1.17
" The dose-response relationships for hepatic CYP2B induction by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) were examined in the male F344/NCr rat."	( Dose-response relationships for the induction of P450 2B by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzne (TCPOBOP) in rat and cultured rat hepatocytes. Dragnev, KH; Jones, CR; Lubet, RA; Mellini, DW; Nims, RW; Sinclair, JF; Sinclair, PR; Thomas, PE, 1993)	0.29
" However, there are no dose-response studies to address the relationship between induction of hepatic UDP-GT and alteration in thyroid homeostasis."	( Alteration of thyroid homeostasis by UDP-glucuronosyltransferase inducers in rats: a dose-response study. Barter, RA; Klaassen, CD; Liu, J; Liu, Y, 1995)	0.29
" Multiplicities decreased in the order Ar-1254 > PB > DDT, indicating that Ar-1254 was more potent than either PB or DDT at the dosage levels used."	( Dissimilar frequency of hepatoblastomas and hepatic cystadenomas and adenocarcinomas arising in hepatocellular neoplasms of D2B6F1 mice initiated with N-nitrosodiethylamine and subsequently given Aroclor-1254, dichlorodiphenyltrichloroethane, or phenobarb Diwan, BA; Kurata, Y; Rice, JM; Ward, JM, )	0.13
" Dose-response experiments performed with 5-ethyl-5-phenylhydantoin indicated that the intrinsic CYP2B-inducing activity of this congener was as great as that of phenobarbital in the mouse, although a fourfold greater dietary concentration of this hydantoin (2000 ppm) was required to elicit a response equivalent to that caused by 500 ppm phenobarbital."	( Hepatic cytochrome P450 2B induction by ethyl/phenyl-substituted congeners of phenobarbital in the B6C3F1 mouse. Diwan, BA; Lubet, RA; Mellini, DW; Nims, RW; Thomas, PE; Utermahlen, WE, 1994)	0.71
" In this case, it seems necessary to diminish the interval between injections than to give higher dosage in order to maintain plasma concentrations."	( Do enzyme inducers modify haloperidol decanoate rate of release? Agenet, C; Barges-Bertocchio, MH; Levron, JC; Pupeschi, G, 1994)	0.29
" AMD activity at 48 hr after dosing of PB in the ET-treated rats was increased in the same degree as that in the control (normal)."	( Effects of phenobarbital on drug metabolizing enzyme activities and other biochemical parameters in rats with DL-ethionine-induced liver injury. Fujitsuka, T; Honda, K; Kawai, Y; Noguchi, M, 1994)	0.68
" A dose-response curve shows that phenobarbital possibly acts on two different sites, with different affinity constants and stoichiometries."	( Opening of frog skin sodium channels by phenobarbital. Ferreira, KT; Fonseca, PD; Moura, TF, )	0.68
"The dose-response relationship of commercially available preparations of methohexital, pentobarbital, phenobarbital, and thiopental and their respective drug-free solutions on granulocyte function was investigated to evaluate whether suppression of neutrophil chemiluminescence is mediated by the barbiturates themselves or by their drug-free solutions."	( Do barbiturates impair zymosan-induced granulocyte function? Birkhahn, A; Buhl, R; Mirow, N; Schneider, M; Weiss, M; Wernet, P, 1994)	0.5
"The dose-response effects of the four barbiturates on granulocyte function were tested by zymosan-induced neutrophil chemiluminescence and, in addition, in a cell-free chemiluminescence system."	( Do barbiturates impair zymosan-induced granulocyte function? Birkhahn, A; Buhl, R; Mirow, N; Schneider, M; Weiss, M; Wernet, P, 1994)	0.29
" Dose-response comparison of RG 7152 with the tetrazole-substituted leukotriene D4 antagonist LY 171883 to be slightly more potent than RG 7152."	( Induction of peroxisomal enzymes by a tetrazole-substituted 2-quinolinylmethoxy leukotriene D4 antagonist. Groth-Watson, A; Kelley, M; Knoble, D; Kornbrust, D, 1994)	0.29
"The dose-response relationship of four commercially available barbiturates (methohexitone, pentobarbitone, phenobarbitone and thiopentone) and of their drug-free solutions on the production of oxygen radicals by neutrophils were tested by N-formylmethionyl-leucyl-phenylalanine (FMLP)-induced granulocyte chemiluminescence and in a cell-free chemiluminescence system."	( Do barbiturates and their solutions suppress FMLP-induced neutrophil chemiluminescence? Birkhahn, A; Buhl, R; Mirow, N; Schneider, M; Weiss, M; Wernet, P, 1994)	0.29
" Overall, the data provide no support for the view that the degree of discriminability of a drug is an indicator of potential state-dependency effects and is restricted only to the dosage high enough to produce noticeable intoxication."	( Phenytoin and phenobarbital: a comparison of their state-dependent effects. Karanth, KS; Kumar, KB; Ramalingam, S, 1994)	0.65
" Serial (US) examination after the administration of phenobarbital as a cholagogue at a dosage of 5 mg/kg/day for 5 days was performed to evaluate nine patients with neonatal jaundice."	( Effect of phenobarbital on serial ultrasonic examination in the evaluation of neonatal jaundice. Ikeda, S; Ogawa, M; Sera, Y; Yamamoto, H, )	0.78
" Upon instituting felbamate, valproate dosage was reduced to 500 mg/d and phenobarbital to 200 mg/d."	( Potential pharmacokinetic interaction between felbamate and phenobarbital. Gidal, BE; Zupanc, ML, 1994)	0.76
" Rats receiving phenobarbital had therapeutic concentrations during most of the 24-hour dosing period, but also experienced supratherapeutic peak concentrations."	( Phenobarbital modifies seizure-related brain injury in the developing brain. Chronopoulos, A; Gatt, A; Holmes, GL; Hyde, P; Liu, Z; Mikati, MA; Stafstrom, CE; Thurber, S; Werner, S, 1994)	2.08
" The effect of pretreatment of rats with various inhibitors and inducers of cytochrome P450 on these dose-response relationships was investigated."	( Influence of inducers and inhibitors of cytochrome P450 on the hepatotoxicity of hydrazine in vivo. Jenner, AM; Timbrell, JA, 1994)	0.29
", labeling during Days 1-3) of dosing with 80 mg/kg/day phenobarbital."	( Phenobarbital-induced hepatocellular proliferation: anti-bromodeoxyuridine and anti-proliferating cell nuclear antigen immunocytochemistry. Barrass, NC; Clarke, NA; Jones, HB, 1993)	1.97
"The dose-response characteristics of initiation of hepatocarcinogenesis by diethylnitrosamine (DEN) was investigated in the neonatal female rat by means of the quantitative stereologic estimation of altered hepatic foci (AHF) expressing multiple markers."	( The effect of the dose of diethylnitrosamine on the initiation of altered hepatic foci in neonatal female rats. Dragan, YP; Pitot, HC; Xu, YH, 1993)	0.29
" Creatinine concentrations should not be considered when dosage adjustments of renally eliminated drugs are being calculated for patients with such metabolic interferences."	( Creatinine metabolism impairment by an anticonvulsant drug, phenacemide. Baltassat, P; Cahen, R; Francois, B; Louisot, P; Martin, A, 1994)	0.29
" Peak plasma and tissue concentrations were seen at 5 minutes after dosing except for the small intestine (4 hrs) and abdominal fat, stomach and large intestine (4 hrs)."	( Disposition and metabolism of Ro 24-4736 in the rat. Anastasi, EM; Chang, D; Liberato, DJ; Loh, AC; Sasso, GJ; Williams, TH, 1994)	0.29
" These results should be taken into consideration to determine the optimal CCl4 dosing schedule in the rat CCl4-induced cirrhosis model."	( Mechanism of carbon tetrachloride autoprotection: an in vivo study based on 13C-aminopyrine and 13C-galactose breath tests. Brazier, JL; Géloën, A; Minaire, Y; Mion, F; Rousseau, M, 1994)	0.29
" As a result of BR treatment, the PB dosage was reduced in eight dogs (35%)."	( Bromide therapy in refractory canine idiopathic epilepsy. Fenner, WR; Podell, M, )	0.13
" Three months before admission, this dosage was increased to 300 mg/d and phenobarbital (PB) 100 mg/d was added because the seizures were incompletely controlled."	( Valproate-induced coma: case report and literature review. Clavería, LE; Coria, F; Duarte, J; Fernandez, E; Macias, S, 1993)	0.52
" Thus, bicuculline not only produced a rightward shift of the dose-response curves of the central depressant drugs in the cortex, but also increased the maximal stimulation of 35S-TBPS binding."	( Bicuculline-produced regional differences in the modulation of 35S-TBPS binding by GABA, pentobarbital and diazepam in mouse cerebellum and cortex. Liljequist, S; Tabakoff, B, 1993)	0.29
" The t 1/2 and AUC values of PB were significantly increased by ZNS coadministration, and a significant decrease in the Vd/F value of PHT was observed after multiple dosing of ZNS."	( Pharmacokinetic interaction of zonisamide in rats. Effect of zonisamide on other antiepileptics. Fukuchi, H; Kimura, M; Kimura, Y; Kitaura, T; Miyake, K; Tanaka, N, 1993)	0.29
"The formation of paramagnetic chromium in the liver of male mice dosed with K2Cr2O7 (10, 20, and 40 mg Cr/kg) by a single ip injection was investigated by electron spin resonance (ESR) spectrometry."	( Formation of paramagnetic chromium in liver of mice treated with dichromate (VI). Furukawa, Y; Sugiyama, M; Susa, N; Ueno, S, 1995)	0.29
"Bromide toxicosis was diagnosed in an 8-year-old Labrador Retriever that had been treated for epilepsy with potassium bromide, at a dosage of 29 mg/kg of body weight/d."	( Bromide toxicosis secondary to renal insufficiency in an epileptic dog. Linn, K; Nichols, ES; Trepanier, LA, 1996)	0.29
" High chloride intake increases the elimination of bromide in dogs, leading to higher dosage requirements for bromide in dogs fed high-chloride diets."	( High dietary chloride content associated with loss of therapeutic serum bromide concentrations in an epileptic dog. Center, SA; Garland, S; Shaw, N; Trepanier, LA, 1996)	0.29
" Dose-response paradigms in which tissue repair response is measured as a parallel but opposing effect to toxic injury might be useful in more precise prediction of the ultimate outcome of toxic injury in risk assessment."	( Toxicodynamics of low level toxicant interactions of biological significance: inhibition of tissue repair. Mehendale, HM, 1995)	0.29
" Plasma phenobarbital concentrations during the period of long-term phenobarbital treatment with a fixed dosage by body weight were not significantly affected by pregnancy."	( Effect of pregnancy on plasma phenobarbital concentrations in rats. Domoto, H; Furuno, K; Gomita, Y; Kawasaki, H; Moriyama, M; Oishi, R; Yamashita, S, 1995)	1.01
" The use of a combined PB/beta NF induction regime using oral dosing is therefore considered to be a suitable substitute for Aroclor 1254."	( Evaluation of phenobarbital/beta-naphthoflavone as an alternative S9-induction regime to Aroclor 1254 in the rat for use in in vitro genotoxicity assays. Callander, RD; Clay, P; Elcombe, CR; Elliott, BM; Mackay, JM, 1995)	0.65
" Dose-response curves were determined for pentobarbital (twice), methamphetamine, phencyclidine, chlordiazepoxide, and the combination of pentobarbital and the barbiturate antagonist bemegride."	( Drug discrimination under a concurrent schedule. McMillan, DE; Snodgrass, SH, 1996)	0.29
"05), compared with mice dosed with CBZ alone (1,000 mg/kg/day)."	( Effect of treatment with phenobarbital and stiripentol on carbamazepine-induced teratogenicity and reactive metabolite formation. Amore, BM; Bajpai, M; Bennett, GD; Finnell, RH; Levy, RH; Slattery, JT, 1995)	0.59
" The daily dosage of each drug was held constant during treatment of the obesity."	( Clearance of phenytoin and valproic acid is affected by a small body weight reduction in an epileptic obese patient: a case study. Ashikari, Y; Chiba, S; Kodama, Y; Kuranari, M; Sakata, T; Takeyama, M, 1996)	0.29
" A similar pattern of biochemical events has been observed to occur during dosed feed treatment with phenobarbital."	( Biochemical effects of the mouse hepatocarcinogen oxazepam: similarities to phenobarbital. Cunningham, ML; Dudley, CN; Griffin, RJ, 1996)	0.74
" A drug concentration, however, can only be regarded as a guide around which to alter the dosage according to the patient's clinical condition."	( Optimisation of antiepileptic drug therapy. The importance of serum drug concentration monitoring. Yukawa, E, 1996)	0.29
" The aim of this study was to evaluate which dosage of PHT can maintain the therapeutic range in the early postoperative period."	( Peri-operative prophylaxis with phenytoin: dosage and therapeutic plasma levels. Boselli, L; Levati, A; Savoia, G; Tommasino, C; Zoppi, F, 1996)	0.29
" When PB in the dosage of 30-60 mg/d was used in combination with PHT the above mentioned changes were not observed."	( Brainstem auditory evoked potentials in epileptics on different anti-epileptic drugs. Gupta, HL; Mukhopadhyay, S; Panjwani, U; sel Vamurthy, W; Singh, SH; Thakur, L, 1996)	0.29
" In this study, we orally dosed rats with twice the LD50 of metaldehyde following no pretreatment (control) or pretreatment with 1 of 3 different cytochrome P-450 inducers either phenobarbital or o,p'-DDD (inducers of cytochromes P-450 IIB and IIIA) or 3-methylcholanthrene (an inducer of P-450 IA)."	( Phenobarbital-type P-450 inducers protect rats against metaldehyde toxicity. de Saqui-Sannes, P; Fargier, C; Petit, C; Tardieu, D; Thouvenot, N, 1996)	1.93
" The purpose of this work was to characterize the profile and dose-response relationship of microsomal enzyme induction following exposure to MX."	( Induction and inhibition of mouse cytochrome P-450 2B enzymes by musk xylene. Caudill, D; Johnson, DR; Lehman-McKeeman, LD, 1997)	0.3
"The dose-response relationship between liver tumor promoting activity and cytochrome P-450 (CYP) induction by phenobarbital sodium (PB) was investigated using the liver medium-term bioassay system of Ito."	( Dose-related increases in quantitative values for altered hepatocytic foci and cytochrome P-450 levels in the livers of rats exposed to phenobarbital in a medium-term bioassay. Fukushima, S; Funae, Y; Hagiwara, A; Imaoka, S; Kitano, M; Matsuda, T; Shirai, T; Takesada, Y; Tamano, S, 1996)	0.71
" Hair was collected from the back 14 days after beginning the 5-day dosing protocol and analyzed by gas chromatography/mass spectrometry (GC/MS) for codeine and phenobarbital."	( A comparison of phenobarbital and codeine incorporation into pigmented and nonpigmented rat hair. Gygi, SP; Rollins, DE; Wilkins, DG, 1997)	0.84
" In this article, we consider statistical tests for increasing trend in mutant frequency with increasing dose, along with statistical models that may be used to describe the observed dose-response relationships."	( Statistical analysis of the lacI transgenic mouse mutagenicity assay. Fung, KY; Krewski, D; Lutz, WK; Shephard, S; Zhu, Y, 1997)	0.3
" At extremely long half-lives, relative to the period of dosing being monitored, sensitivity approaches 100% if measurement error is in the 1-2% range."	( A computer model for the measurement of compliance using a dual tracer technique. McDonald, J; Shine, D, 1997)	0.3
" When dosed orally to phenobarbital (PB)-treated mice, MX (200 mg/kg) inhibited > 90% of the PB-induced O-dealkylation of 7-pentoxyresorufin (PROD), and [14C]MX equivalents bound covalently to microsomal proteins."	( Mechanism-based inactivation of mouse hepatic cytochrome P4502B enzymes by amine metabolites of musk xylene. Caudill, D; Johnson, DR; Lehman-McKeeman, LD; Stuard, SB, 1997)	0.61
" Thus, the dosage of digitoxin appears to be fully compensated during concomitant use of phenobarbital, but obviously deserves attention during concomitant use of phenytoin or carbamazepine."	( [Serum digitoxin in concomitant use of antiepileptics in routine therapy]. Aass, H; Johannessen, SI; Osnes, JB; Skomedal, T; Stokke, KT, 1997)	0.52
" Separate groups of mice were given phenobarbital (PB) parenterally by intraperitoneal injection at a dosage of 160 mg/kg/day for 3 days."	( Opposite effects of 2,2',4,4',5,5'-hexachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo-p-dioxin on the antibody response to sheep erythrocytes in mice. Birnbaum, LS; DeVito, MJ; Riddle, MM; Smialowicz, RJ; Williams, WC, 1997)	0.57
"5-year-old child receiving phenobarbital for a history of seizures while on continuous cycling peritoneal dialysis (CCPD) had persistent subtherapeutic serum levels despite progressive dosage increases."	( Removal of phenobarbital during continuous cycling peritoneal dialysis in a child. Heilliczer, J; John, EG; Porto, I, )	0.82
" To evaluate the ability of MK to induce cytochromes P450, mice were dosed daily by oral gavage at dosages ranging from 5 to 500 mg/ kg MK for 7 days."	( Characterization of the effects of musk ketone on mouse hepatic cytochrome P450 enzymes. Caudill, D; Lehman-McKeeman, LD; Stuard, SB, 1997)	0.3
" A secondary goal was to compare the effects produced by Telazol and its constituents with those elicited by sodium phenobarbital (PB) using the same dosing regimen."	( Induction of hepatic cytochrome P450 2B and P450 3A isozymes in rats by zolazepam, a constituent of Telazol. Bandiera, SM; Wong, A, 1998)	0.51
" The exanthem disappeared parallel to a dose reduction of phenobarbital and with a gradually increasing dosage up to a maintenance dose of 200 mg."	( [Successful induction of tolerance in an epilepsy patient with phenobarbital allergy]. Fröscher, W; Kleinhans, D, 1998)	0.78
" Male and female Sprague-Dawley (CD) rats were dosed with either pregnenolone-16alpha-carbonitrile (PCN; 50 mg/kg per day for 5 days), phenobarbital (PB; 100 mg/kg per day for 4 days), beta-naphthoflavone (betaNF; 100 mg/kg per day for 3 days), clofibrate (CF; 300 mg/kg per day for 14 days), isoniazid (ISO; 100 mg/kg per day for 3 days), or dexamethasone (DEX; 50 mg/kg per day for 4 days)."	( Ethylmorphine N-demethylase activity as a marker for cytochrome P450 CYP3A activity in rat hepatic microsomes. Amacher, DE; Schomaker, SJ, 1998)	0.5
" For comparison of drug potencies, doses increasing seizure thresholds by 20 or 50% were calculated from dose-response curves."	( Anticonvulsant drug effects in the direct cortical ramp-stimulation model in rats: comparison with conventional seizure models. Krupp, E; Löscher, W, 1998)	0.3
" Phenobarbital is a better discriminant when dosing is every 24 hours as with artesunate, rather than the 8-hourly regimen for quinine-tetracycline."	( Initial evaluation of low-dose phenobarbital as an indicator of compliance with antimalarial drug treatment. Feely, M; Fungladda, W; Hay, A; Karbwang, J; Pickard, CE; Shires, S, 1998)	1.5
" Adverse cardiovascular and neurologic effects for each drug, dosage and route of administration were evaluated."	( Chronic phenobarbital therapy reduces plasma benzodiazepine concentrations after intravenous and rectal administration of diazepam in the dog. Podell, M; Sams, RA; Wagner, SO, 1998)	0.73
" From our experience, careful and individual dosing of fosphenytoin in this age group can be considered."	( Fosphenytoin in infants. Caviness, VS; Krishnamoorthy, KS; Soman, TB; Takeoka, M, 1998)	0.3
"5-2-fold increases in the induction magnitude of CYP2B1 and CYP2B2 mRNA expression resulting from PB exposures, without altering the bell-shaped dose-response curve characteristic of this agent."	( Insulin-mediated modulation of cytochrome P450 gene induction profiles in primary rat hepatocyte cultures. Omiecinski, CJ; Sidhu, JS, 1999)	0.3
" The present study was designed to examine the dose-response effect of TSH-increasing (PB and PCN) and nonincreasing (3MC and PCB) UDP-GT inducers on apoptosis and TGF-beta1."	( Dose-response examination of UDP-glucuronosyltransferase inducers and their ability to increase both TGF-beta expression and thyroid follicular cell apoptosis. Klaassen, CD; Kolaja, KL, 1998)	0.3
" A dose-dependent induction of each endpoint was observed, although plateaus in the various dose-response curves were not obtained, and ED50 values (PB concentrations associated with half-maximal responses) for the various endpoints were not able to be calculated."	( Dose-response relationships for cytochrome P450 induction by phenobarbital in the cotton rat (Sigmodon hispidus). Henneman, JR; Jones, CR; Lubet, RA; Nims, RW, 1998)	0.54
" The public health implication of this lack of linearity in the low-dose area of the dose-response curve raises the question of whether low doses of carcinogens will reduce cancer risk."	( Can the concept of hormesis Be generalized to carcinogenesis? Baldwin, LA; Calabrese, EJ, 1998)	0.3
"Plasma concentrations of lamotrigine, an antiepileptic drug obtained in three adult controlled clinical trials conducted in the United States were pooled and analyzed using NONMEM, a population pharmacokinetic computer program, to facilitate development of dosing guidelines."	( Population pharmacokinetics of lamotrigine adjunctive therapy in adults with epilepsy. Chen, C; Cox, E; Fiedler-Kelly, J; Grasela, TH; Risner, ME; Womble, GP, 1999)	0.3
" Transfected cells were dosed with several known inducers of CYP3A4 and the levels of SPAP were measured."	( A reporter gene assay to assess the molecular mechanisms of xenobiotic-dependent induction of the human CYP3A4 gene in vitro. Gibson, GG; Goldfarb, PS; Gray, TJ; Ogg, MS; Tarbit, M; Williams, JM, 1999)	0.3
"To describe the dosing and pharmacokinetics of phenobarbital in a neonate receiving extracorporeal membrane oxygenation (ECMO)."	( Phenobarbital dosing and pharmacokinetics in a neonate receiving extracorporeal membrane oxygenation. Buck, ML; Elliott, ES, 1999)	2
"The effect of recombinant human interleukin-1beta (IL-1beta) on the modulation of hepatic cytochrome P450 (P450) was investigated by in vivo subcutaneous dosing studies in male Sprague-Dawley rats."	( Role of interleukin-1beta in the modulations of cytochrome P450 and heme metabolism in rat liver. Kawano, K; Kudo, S, 1999)	0.3
" Valproate, when the proper therapeutic dosage was belatedly realized, was seen as a superior treatment for generalized and partial epilepsies."	( Clinical experience with new antiepileptic drugs: antiepileptic drugs in Europe. Loiseau, PJ, 1999)	0.3
" Because dosing is often modest, cost should rarely be the overriding factor in choosing a drug for a patient with newly diagnosed epilepsy in the developed world."	( Monostars: an aid to choosing an antiepileptic drug as monotherapy. Brodie, MJ, 1999)	0.3
" Further studies are required to establish its role and the optimal dosage regimen of charcoal to be administered."	( Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. , 1999)	0.3
" They then fitted those altered levels to the dosing pattern most likely to have produced them, given known kinetics of the tracers."	( Limits of confidence in tracer compounds as a means of measuring patient compliance with medication. McDonald, J; Shine, D, 1999)	0.3
" In one group, dosage was adjusted to achieve serum AED concentration within a target range (10-20 microg/ml for PHT, 15-40 microg/ml for PB, 4-11 microg/ml for CBZ, and 40-100 microg/ml for VPA), whereas in the other group, dosage was adjusted on clinical grounds."	( A multicenter randomized controlled trial on the clinical impact of therapeutic drug monitoring in patients with newly diagnosed epilepsy. The Italian TDM Study Group in Epilepsy. Bartoli, A; Cian, P; Fattore, C; Gatti, G; Jannuzzi, G; Monaco, F; Perucca, E, 2000)	0.31
" In conclusion, although the phenobarbital dose of 20 mg/kg given to children with cerebral malaria provides highly effective seizure prophylaxis, an unacceptable increase in mortality is noted; hence, use of this dosage is not recommended."	( Effect of phenobarbital on seizure frequency and mortality in childhood cerebral malaria: a randomised, controlled intervention study. Crawley, J; Marsh, K; Mithwani, S; Mwangi, I; Ouma, D; Peto, T; Waruiru, C; Watkins, W; Winstanley, P, 2000)	1
"A capillary electrophoresis method was developed to separate and quantitate ephedrine (ED), theophylline (TP) and phenobarbital (PB) in a tablet dosage form."	( Determination of ephedrine, theophylline and phenobarbital in a tablet dosage form by capillary electrophoresis. Haque, A; Stewart, JT; Xu, X, 1999)	0.77
" After lamotrigine was added for better seizure control and the dosage of gabapentin was tapered, anorgasmia improved."	( Improved sexual function in three men taking lamotrigine for epilepsy. Carwile, ST; Husain, AM; Miller, PP; Radtke, RA, 2000)	0.31
"Phenobarbitone does not interfere with LDDS testing regardless of dosage or treatment time."	( Effect of phenobarbitone on the low-dose dexamethasone suppression test and the urinary corticoid: creatinine ratio in dogs. Church, DB; Foster, SF; Watson, AD, 2000)	0.31
"Phenobarbital (PB) was shown to induce the major PB-inducible cytochrome P450 (CYP) isoforms, CYP2B1/2, in perivenular hepatocytes by a single injection, and in midzonal and periportal hepatocytes in addition to perivenular hepatocytes by injections of the same dosage once a day for 3 days in rat livers."	( Effect of phenobarbital on intralobular expression of CYP2B1/2 in livers of rats: difference in the expression between single and repetitive administrations. Kanamura, S; Mondo, H; Takamori, Y; Takeda, K; Watanabe, J, 2000)	2.15
" Experimental studies in pregnant rabbits using Primatene in both low and high dosage resulted in limb reduction defects and other malformations in a significant number of the offspring compared with controls."	( Association of sympathomimetic drugs with malformations. Drut, RM; Gilbert-Barness, E, 2000)	0.31
"All three oral dosage forms of phenobarbital are bioequivalent."	( Oral bioavailability of phenobarbital: a comparison of a solution in Myvacet 9-08, a suspension, and a tablet. Bosch, FH; Essink, GW; Lankhaar, G; van Sorge, AA; Yska, JP, 2000)	0.9
" Individual optimal drug dosage can be calculated for each patient at little cost to the pet owner."	( Drug choice and therapeutic drug monitoring in the management of canine primary epilepsy. Taylor, JH; Vaughan-Scott, T, 1999)	0.3
"To determine whether there are therapeutically relevant changes in serum phenobarbital concentrations throughout a daily dosing interval in epileptic dogs receiving phenobarbital for > or = 3 weeks."	( Effect of timing of blood collection on serum phenobarbital concentrations in dogs with epilepsy. Levitski, RE; Trepanier, LA, 2000)	0.8
"There is no therapeutically relevant change in serum phenobarbital concentrations throughout a daily dosing interval in most epileptic dogs."	( Effect of timing of blood collection on serum phenobarbital concentrations in dogs with epilepsy. Levitski, RE; Trepanier, LA, 2000)	0.81
" Drug dosage must be reevaluated if a dog's diet, body weight, or body composition changes during treatment."	( Effects of diet on pharmacokinetics of phenobarbital in healthy dogs. Fettman, MJ; Greco, DS; Maguire, PJ; Ogilvie, GK; Smith, MO; Turner, AS; Walton, JA, 2000)	0.58
" Therapy with primidone was started at a dosage of 500 mg/day, and the phenobarbital was stopped."	( The "forgotten" cross-tolerance between phenobarbital and primidone: it can prevent acute primidone-related toxicity. Frey, M; Kanner, AM; Parra, J, 2000)	0.81
" Increasing doses of ketamine were administered 60 min after stimulation to generate a dose-response curve."	( Ketamine controls prolonged status epilepticus. Bertram, EH; Borris, DJ; Kapur, J, 2000)	0.31
" In these patients SHS developed during the first 7 months of therapy and regressed after PB discontinuation or, in 2 cases, after dosage reduction."	( Shoulder-hand syndrome in neurosurgical patients treated with barbiturates. A long term evaluation. Bello, L; Ceccarelli, G; Cesana, BM; De Santis, A; Spagnoli, D; Villani, RM, 2000)	0.31
") for 6 weeks to female lambda/lacI transgenic rats caused a 4-fold increase in mutation frequency (MF) at the lacI gene locus in the livers of dosed animals compared with controls."	( Tamoxifen mutagenesis and carcinogenesis in livers of lambda/lacI transgenic rats: selective influence of phenobarbital promotion. Davies, R; Fenwick, S; Smith, LL; Styles, JA; Walker, J; White, IN, 2001)	0.52
" Weanling male CD rats (21 days old) were dosed for 30 d by gavage with vehicle (0."	( Evaluation of the male pubertal assay's ability to detect thyroid inhibitors and dopaminergic agents. Carney, EW; Crissman, JW; Marty, MS, 2001)	0.31
" Additionally, data concerning time- and dose-response induction of ALDH1A3 after phenobarbital and griseofulvin treatment are presented."	( Phenobarbital inducibility and differences in protein expression of an animal model. Karamanakos, P; Marselos, M; Pappas, P; Stephanou, P; Vasiliou, V, 2001)	1.98
" Rats were either pretreated with phenobarbital (PB) or left untreated and then dosed with alpha-HCH."	( Understanding enantioselective processes: a laboratory rat model for alpha-hexachlorocyclohexane accumulation. Bigsby, RM; Caperell-Grant, A; Hites, RA; Ulrich, EM; Willett, KL, 2001)	0.59
" As the novel microphysiometer works under regular cell culture conditions, cells can be repeatedly simulated with drugs to complete dose-response curve within a few hours."	( A novel microphysiometer based on MLAPS for drugs screening. Ping, W; Qingtao, Z; Rong, L; Weimin, Y; Xiaoxiang, Z; Xuesong, Y; Yicong, W, 2001)	0.31
" The correlation between carbamazepine clearance and patient-specific characteristics may thus allow dosage adjustment to be made to achieve target steady-state plasma concentrations."	( Population pharmacokinetics of carbamazepine in Singapore epileptic patients. Chan, E; Hue, SS; Lee, HS, 2001)	0.31
" We have examined the dose-response relationship of tamoxifen-induced DNA adducts in the liver and the subsequent increase in the development of liver cancer, with and without phenobarbital promotion."	( Cumulative exposure to tamoxifen: DNA adducts and liver cancer in the rat. Carthew, P; Edwards, RE; Heydon, RT; Lee, PN; Martin, EA; Nolan, BM, 2001)	0.5
" Four doses, administered at 2 h intervals, of 15 mg/kg (4x15 mg/kg) D-METH significantly decreased TH and dopamine levels to 50% of control in mice becoming hypothermic during dosing in a 13 degrees C environment."	( Phenobarbital and dizocilpine can block methamphetamine-induced neurotoxicity in mice by mechanisms that are independent of thermoregulation. Bowyer, JF; Holson, RR; Miller, DB; O'Callaghan, JP, 2001)	1.75
" Oral high-dose phenobarbital therapy was begun at a dosage of 15 mg/kg/day, and the seizures markedly decreased to 5-10 times per day and the epileptic discharges on electroencephalogram greatly decreased."	( Oral high-dose phenobarbital therapy for early infantile epileptic encephalopathy. Kawada, Y; Noma, S; Ozawa, H; Sugai, K, 2002)	1.01
" Further detailed pharmacokinetic studies of irinotecan in patients receiving concomitant therapy with enzyme-inducing anticonvulsants are required so that rational dosing recommendations can be provided for this patient population."	( Influence of phenytoin on the disposition of irinotecan: a case report. Berg, S; Bernstein, M; Blaney, SM; Cherrick, I; Kuttesch, N; Murry, DJ; Salama, V, 2002)	0.31
" An antibody raised against CYP2B1 markedly inhibited the PCB-dependent bilirubin degradation and PROD activities of phenobarbital-induced microsomes with similar dose-response curves for the two effects."	( Bilirubin and uroporphyrinogen oxidation by induced cytochrome P4501A and cytochrome P4502B. Role of polyhalogenated biphenyls of different configuration. Dawson, SJ; De Matteis, F; Pipino, S; Pons, N, 2002)	0.52
" In order to demonstrate the major advantage of these tool for studying gene expression, samples of control rat liver were compared with those of animals dosed with phenobarbital (PB) or pregnenolone-16 alpha-carbonitrile (PCN), two compounds well known to induce cytochrome P450 isoforms of 2B and 3A subfamilies, respectively."	( Gene expression profiling of drug metabolism and toxicology markers using a low-density DNA microarray. Bertholet, V; Chandelier, N; de Longueville, F; Evrard, S; Le Bourdellès, B; Meneses-Lorente, G; Pike, A; Rasson, JP; Remacle, J; Surry, D; Talbot, V; Worboys, P, 2002)	0.51
"The purpose of this study was to investigate the relationship of changes in the enzyme-inducing anticonvulsant daily dosage (drug score) to variations in urinary D-glucaric acid excretion and gamma-glutamyltransferase and beta-glucuronidase serum activities."	( Relationship between changes in drug score, D-glucaric acid excretion, and gamma-glutamyltransferase and beta-glucuronidase serum activities during anticonvulsant treatment. Fernández, MP; Hermida, J; Tutor, JC, 2002)	0.31
" For the current studies, male rats were dosed for 15 days via oral gavage and euthanized on the morning of test day 15."	( Evaluation of a 15-day screening assay using intact male rats for identifying steroid biosynthesis inhibitors and thyroid modulators. Frame, SR; Ladics, GS; O'Connor, JC, 2002)	0.31
" The developed method is rapid and sensitive and therefore suitable for routine control of these drugs in dosage form."	( HPLC assay of acetylsalicylic acid, paracetamol, caffeine and phenobarbital in tablets. Agbaba, D; Aleksic, M; Eric, S; Franeta, JT; Pavkov, S; Vladimirov, S, 2002)	0.56
" The objectives were: education for the patient, family, and village leaders in orders to achieve good compliance, uninterrupted supply of generic phenobarbitol, follow-up visits once a month for one year then every two months if good compliance with a country physician with delivery of phenobarbitol in sufficient quantity to reach the next visit, verification of correct drug dosage and use, supervision of treatment effect."	( [Treatment of epilepsy in rural areas in Mali]. Desplats, D; Doumbo, O; Farnarier, G; Nimaga, K, 2002)	0.31
"To establish a dosing regimen for potassium bromide and evaluate use of bromide to treat spontaneous seizures in cats."	( Disposition and clinical use of bromide in cats. Boothe, DM; Couch, P; George, KL, 2002)	0.31
" Role of prophylactic postnatal phenobarbitone (two different dosage regimens) was evaluated prospectively on occurrence of neonatal jaundice and the need for therapy in 150 babies with birth weight 1000-1499 grams."	( Phenobarbitone prophylaxis for neonatal jaundice in babies with birth weight 1000-1499 grams. Garewal, G; Kumar, P; Kumar, R; Narang, A, 2002)	0.31
" The chemicals were found to differ characteristically in their potency and dose-response relationship to induce FAH when given alone or when administered following initiation with diethylnitrosamine."	( Prevalidation of a rat liver foci bioassay (RLFB) based on results from 1600 rats: a study report. Bannasch, P; Brendler-Schwaab, S; Deml, E; Enzmann, H; Haertel, T; Ittrich, C; Kopp-Schneider, A; Küttler, K; Mellert, W; Mönnikes, O; Oesterle, D; Schladt, L; Schwarz, M, )	0.13
" The difficulty in achieving therapeutic dosage because of side effects makes one consider whether these agents are "better" than the oldest and most side effect-prone AED, phenobarbital."	( Clinical pharmacology of topiramate versus lamotrigine versus phenobarbital: comparison of efficacy and side effects using odds ratios. Claycamp, HG; Lathers, CM; Schraeder, PL, 2003)	0.75
" No dosage adjustment is likely to be necessary when retigabine and phenobarbitone are coadministered to patients."	( Lack of pharmacokinetic interaction between retigabine and phenobarbitone at steady-state in healthy subjects. Ferron, GM; Parks, V; Patat, A; Rolan, P; Troy, SM, 2003)	0.32
" Group 1 (n = 48), group 2 (n = 29), and group 3 (n = 18) received phenobarbital at the dosage of 5 mg/kg/day for at least 5 days, less than 5 mg/kg/day or less than 5 days, and no premedication, respectively."	( The effect of phenobarbital on the accuracy of technetium-99m diisopropyl iminodiacetic acid hepatobiliary scintigraphy in differentiating biliary atresia from neonatal hepatitis syndrome. Charearnrad, P; Chongsrisawat, V; Poovorawan, Y; Tepmongkol, S, 2003)	0.92
" Excessive drowsiness can be avoided by proper dosage and proper timing of drug administration."	( Treatment of epilepsy. BAILEY, AA, 1963)	0.24
"Prior administration of phenobarbitone to male and female rats dosed orally or intravenously with griseofulvin caused a fall in blood levels of the antibiotic."	( AN EFFECT OF PHENOBARBITONE ON GRISEOFULVIN METABOLISM IN THE RAT. BUSFIELD, D; CHILD, KJ; TOMICH, EG, 1964)	0.24
" Groups 3 and 5 were fed melatonin-containing diet for 20 wk, starting 1 wk after the last dosing of DEN."	( Chemopreventive effects of melatonin on diethylnitrosamine and phenobarbital-induced hepatocarcinogenesis in male F344 rats. Mori, H; Rahman, KM; Sugie, S; Tanaka, T; Watanabe, T, 2003)	0.56
" Prolonged oral administration with twice-daily dosing of ELB 138 with either 5 or 40 mg/kg over a 5-week period was not associated with loss of anticonvulsant efficacy in the PTZ dog model."	( Anticonvulsant efficacy of the low-affinity partial benzodiazepine receptor agonist ELB 138 in a dog seizure model and in epileptic dogs with spontaneously recurrent seizures. Löscher, W; Potschka, H; Rieck, S; Rundfeldt, C; Tipold, A, 2004)	0.32
" CBZ, PB, OXC, and VPA displayed a dose-response relation."	( Fracture risk associated with use of antiepileptic drugs. Mosekilde, L; Rejnmark, L; Vestergaard, P, 2004)	0.32
" PB produced a twofold increase in liver MF over controls after 27 weeks of treatment, but a similar increase was not observed with longer dosing times; at later time points, the MF in the PB groups was lower than that of the control group, suggesting that PB is not producing direct DNA damage in the liver."	( Evaluation of mutant frequencies of chemically induced tumors and normal tissues in lambda/cII transgenic mice. de Boer, J; Fairchild, D; Glickman, B; Johnson, A; Kanazawa, N; Mirsalis, JC; Nguyen, T; Shimon, JA; Winegar, RA, 2005)	0.33
" Because of the differences among inter-individuals in the metabolic clearance of these drugs and their toxicity at certain levels of concentration in serum, the dosage should be regulated to maintain a therapeutic blood drugs level."	( [Simultaneous analysis of theophylline, phenobarbital, amobarbital and carbamazepine in serum by high performance liquid chromatography]. Duan, S; Fu, S; Ren, Q, 1997)	0.56
" However, urinary PAG excretion was similar in rats dosed solely with amiodarone or in combination with phenobarbitone, despite the fact that the degree of phospholipid accumulation was far less in rats given the combined treatment."	( Phenylacetylglycine, a putative biomarker of phospholipidosis: its origins and relevance to phospholipid accumulation using amiodarone treated rats as a model. Delaney, J; Leonard, MS; Miles, A; Neville, WA; Swain, A; Waterfield, CJ, )	0.13
" Here, we describe the use of a differential display technology to understand the molecular mechanisms related to 13 weeks of dosing with the prototype rodent nongenotoxic hepatocarcinogen, phenobarbital."	( Differential display in rat livers treated for 13 weeks with phenobarbital implicates a role for metabolic and oxidative stress in nongenotoxic carcinogenicity. Alden, CL; Blomme, EA; Bunch, RT; Cabonce, MA; Curtiss, SW; Elrick, MM; Kier, LD; Kolaja, KL; Kramer, JA; Morris, DL; Rodi, CP, 2005)	0.76
" Application of the findings in this study to patient care may permit selection of an appropriate initial maintenance dosage to achieve target phenobarbital concentrations, thus enabling the clinician to achieve the desired therapeutic effect in neonates and infants."	( Population pharmacokinetic investigation of phenobarbital by mixed effect modelling using routine clinical pharmacokinetic data in Japanese neonates and infants. Minemoto, M; Suematsu, F; Yukawa, E; Yukawa, M, 2005)	0.79
" Furthermore, our data demonstrated the presence of a threshold for the non-genotoxic carcinogen, phenobarbital (PB), and the lack of linearity in the low-dose area of the dose-response curve, providing evidence for hormesis."	( Current and emerging challenges in toxicopathology: carcinogenic threshold of phenobarbital and proof of arsenic carcinogenicity using rat medium-term bioassays for carcinogens. Fukushima, S; Kinoshita, A; Morimura, K; Salim, EI; Wanibuchi, H, 2005)	0.77
"Patients were stabilised using phenobarbitone and/or potassium bromide to produce tolerable therapeutic serum concentrations and dosed additionally with gabapentin at 35 to 50 mg/kg/d (divided twice or three times daily) for 4 months."	( Improving seizure control in dogs with refractory epilepsy using gabapentin as an adjunctive agent. Govendir, M; Malik, R; Perkins, M, 2005)	0.33
" Linear regression analysis of dose-response relationship between the doses of 2-PMPA and their corresponding threshold values allowed the calculation of threshold increasing dose by 20% (TID20), which was 109."	( 2-phosphonomethyl-pentanedioic acid (glutamate carboxypeptidase II inhibitor) increases threshold for electroconvulsions and enhances the antiseizure action of valproate against maximal electroshock-induced seizures in mice. Czuczwar, SJ; Luszczki, JJ; Mohamed, M, 2006)	0.33
" This study was undertaken to help elucidate dose-response changes in gene expression (transcriptome) in the liver of rats in response to administration of known genotoxic or nongenotoxic liver carcinogens."	( Gene expression dose-response of liver with a genotoxic and nongenotoxic carcinogen. Gollapudi, BB; Kan, HL; Seidel, SD; Sparrow, BR; Stott, WT, )	0.13
" Initially, livers from rats dosed with the prototypic P450 inducers beta-napthoflavone (BNF), phenobarbital (PB), dexamethasone (DEX), and clofibric acid (CLO) were analyzed for mRNA levels of CYP1A1, 1A2, 2B1, 2B2, 2E1, 3A2, 3A23, and 4A1 and compared with control animals."	( Cytochrome P450 gene induction in rats ex vivo assessed by quantitative real-time reverse transcriptase-polymerase chain reaction (TaqMan). Ashby, CA; Ayrton, AD; Baldwin, SJ; Bramhall, JL; Clarke, SE; Hood, SR; Murdock, PR; Yue, L, 2006)	0.55
"05% (wt/wt) PB in drinking water for 2 or 4 weeks, and a 2-week recovery was included following each dosing period."	( Phenobarbital induces progressive patterns of GC-rich and gene-specific altered DNA methylation in the liver of tumor-prone B6C3F1 mice. Bachman, AN; Goodman, JI; Phillips, JM, 2006)	1.78
" Rats were pretreated with PB (75 mg/kg for 4 days) prior to itraconazole or fluconazole dosing (20 and 200 mg/kg for 4 days)."	( Involvement of phenobarbital and SKF 525A in the hepatotoxicity of antifungal drugs itraconazole and fluconazole in rats. Ahmad Bustamam, A; Hasiah, AH; Israf, DA; Khairi, HM; Somchit, N; Sulaiman, MR; Wong, CW; Zuraini, A, 2006)	0.69
" The proposed study could provide the first concrete evidence of treatment efficacy because (1) it examines a homogeneous patient population, (2) the recognition and quantification of seizures rests solely on the gold standard of seizure detection (EEG), and (3) the dosing of phenobarbital is matched specifically to the phenobarbital-binding characteristics of the individual treated."	( Summary proceedings from the neurology group on neonatal seizures. Clancy, RR, 2006)	0.51
"3% had severe side effects when the dosage of phenobarbital in the first 3 months was increased."	( [Evaluation of the efficacy of phenobarbital in treatment of epilepsy in rural areas: study of 2455 patients in rural China]. Dai, XY; Hong, Z; Ma, GY; Wang, TP; Wang, WZ; Wu, JZ; Yang, B; Yuan, CL; Zhao, DH, 2006)	0.88
" I reviewed the charts of 99 patients treated with PB to assess the incidence, clinical characteristics, investigations, dosage and plasma concentration of PB, and risk factors in the development of CRPS-I."	( [Complex regional pain syndrome type I induced by phenobarbital]. Tanabe, Y, 2006)	0.59
" In addition to changes in the hepatic expression of well-characterized drug-metabolizing enzymes, an increase in Mdm2 mRNA was observed with both compounds after single or repeat dosing (5 days)."	( p53-independent induction of rat hepatic Mdm2 following administration of phenobarbital and pregnenolone 16alpha-carbonitrile. Bhaskaran, V; Foster, WR; Lehman-McKeeman, LD; Nelson, DM, 2006)	0.56
" When one compound ofa pharmacologically active substance is replaced by a different compound, the dosage should be corrected for both the chemical structure, such as the molecular weight, and the pharmacokinetic properties such as absorption, metabolism and biological availability."	( [Intoxication due to replacement of the precursor methylphenobarbital by phenobarbital]. Heeringa-Karreman, M; van Munster, ET, 2006)	0.58
" Measuring antiepileptic drug levels in body fluids (therapeutic drug monitoring) is frequently used to optimise drug dosage for individual patients."	( Therapeutic monitoring of antiepileptic drugs for epilepsy. Dahl, ML; Kimland, E; Tomson, T, 2007)	0.34
" In this open study, 180 patients with newly-diagnosed, untreated epilepsy were randomised to treatment with the antiepileptic drug selected by their physician either with or without therapeutic drug serum level monitoring as an aid to dosage adjustments."	( Therapeutic monitoring of antiepileptic drugs for epilepsy. Dahl, ML; Kimland, E; Tomson, T, 2007)	0.34
" Carbamazepine (CBZ) and phenobarbital (PHB) during pregnancy should be used at the lowest dosage compatible with maternal disease."	( Unilateral multicystic dysplastic kidney in infants exposed to antiepileptic drugs during pregnancy. Carta, M; Cimador, M; Corsello, G; De Grazia, E; Di Pace, MR; Giuffrè, M; Sergio, M, 2007)	0.64
"To describe the dose-concentration relationship of a continuous intravenous infusion of valproic acid (VPA) in pediatric patients when a dosing protocol is used."	( Clinical utility of a continuous intravenous infusion of valproic acid in pediatric patients. Baumann, RJ; Cook, AM; Farzam, F; Kuhn, RJ; Lewis, DA; Taylor, LM, 2007)	0.34
" Depending on the intended indication and dosing regimen, PPL can delay or stop development of a compound in the drug discovery process."	( Evaluation of a published in silico model and construction of a novel Bayesian model for predicting phospholipidosis inducing potential. Gehlhaar, D; Greene, N; Johnson, TO; Pelletier, DJ; Tilloy-Ellul, A, )	0.13
" The steady-state plasma concentrations of AEDs at the experimental dosage were coincided with the range of clinical therapeutic concentrations."	( [Experimental study on the possibility of brain damage induced by chronic treatment with phenobarbital, clonazepam, valproic acid and topiramate in immature rats]. Cai, FC; Zhang, XP; Zhu, HX, 2007)	0.56
" In dogs that remained refractory, the dosage was increased to 20 mg/kg TID for 2 months."	( The efficacy and tolerability of levetiracetam in pharmacoresistant epileptic dogs. Chandler, KE; Luján Feliu-Pascual, A; Matiasek, LA; Platt, SR; Volk, HA, 2008)	0.35
"Within the scope of the Rat Liver Foci Bioassay the model carcinogens N-nitrosomorpholine (NNM), 2-acetylaminoflouren (2-AAF), phenobarbital (PB), and clofibrate (CF) were analyzed concerning their potency and dose-response relationship to induce foci of altered hepatocytes (FAHs), which are known to be precursor lesions of liver adenoma and carcinoma."	( Comparison of mode of action of four hepatocarcinogens: a model-based approach. Bannasch, P; Groos, J; Kopp-Schneider, A; Schwarz, M, 2007)	0.55
" The nontoxic HgS dosing (0."	( Attenuation by methyl mercury and mercuric sulfide of pentobarbital induced hypnotic tolerance in mice through inhibition of ATPase activities and nitric oxide production in cerebral cortex. Chang, LH; Chuu, JJ; Huang, ZN; Lin-Shiau, SY; Yu, HH, 2008)	0.35
" PB dosage ranged 40-140 mg/kg/day (mean: 70 mg/kg/day)."	( Very high dose phenobarbital for refractory status epilepticus. Arunpongpaisal, S; Auevitchayapat, N; Chaiyakum, A; Jitpimolmard, S; Mayurasakorn, N; Phunikhom, K; Phuttharak, W; Saengsuwan, J; Suko, P; Tiamkao, S; Vannaprasaht, S, 2007)	0.69
" Four patients experienced relapse with a decreased dosage of valproate."	( Effective prophylactic therapy for cyclic vomiting syndrome in children using valproate. Amakata, K; Fujii, Y; Hikita, T; Kaga, F; Kaneko, S; Kodama, H; Nakamoto, N; Ogita, K; Yanagawa, Y, 2009)	0.35
" Outcome did not depend on duration of barbiturate therapy, dosage or serum concentration, co-medication, reduction rate, degree of intellectual disability, or epilepsy syndrome."	( Ambiguous results of an attempt to withdraw barbiturates in epilepsy patients with intellectual disability. Bocchicchio, M; Hauser, I; Horstmann, V; Huber, B; Jokeit, G; May, T; Meinert, T; Robertson, E; Schorlemmer, H; Schulz, L; Seidel, M; Wagner, W, 2009)	0.35
" A significant relationship was found between body condition score and fasting serum triglyceride concentration in all dogs, but serum triglyceride concentration was not significantly associated with phenobarbital dosage or serum phenobarbital concentration."	( Serum triglyceride concentration in dogs with epilepsy treated with phenobarbital or with phenobarbital and bromide. Govendir, M; Ilkin, WJ; Kluger, EK; Malik, R; Snow, D; Sullivan, DR, 2008)	0.77
" The last dosage of maternal methadone just before delivery and the length of treatment for neonatal abstinence syndrome were examined with an analysis of variance model."	( High-dose methadone in pregnant women and its effect on duration of neonatal abstinence syndrome. Cordero, L; Gardner, DK; Lim, S; Prasad, MR; Samuels, P, 2009)	0.35
"Accurate measurement of the threshold dosage of phenobarbital that can produce drug discrimination (DD) may improve our understanding of the mechanisms and properties of such discrimination."	( Measurement of the lowest dosage of phenobarbital that can produce drug discrimination in rats. Gordon, MK; Overton, DA; Patel, BN; Pragada, SR; Stanwood, GD, 2009)	0.88
"This study aimed to compare three methods for determining the threshold dosage for phenobarbital (D) versus no-drug (N) DD."	( Measurement of the lowest dosage of phenobarbital that can produce drug discrimination in rats. Gordon, MK; Overton, DA; Patel, BN; Pragada, SR; Stanwood, GD, 2009)	0.85
" A titration scheme was employed to increase or decrease dosage at the end of each 18-day block of sessions depending on whether the rat had achieved criterion accuracy during the sessions just completed."	( Measurement of the lowest dosage of phenobarbital that can produce drug discrimination in rats. Gordon, MK; Overton, DA; Patel, BN; Pragada, SR; Stanwood, GD, 2009)	0.63
" In most rats, dosage decreased to low levels and then oscillated near the minimum level required to maintain criterion performance."	( Measurement of the lowest dosage of phenobarbital that can produce drug discrimination in rats. Gordon, MK; Overton, DA; Patel, BN; Pragada, SR; Stanwood, GD, 2009)	0.63
"The lowest discriminated dosage is influenced by the criterion of discriminative control that is employed and is higher than the absolute threshold at which discrimination entirely disappears."	( Measurement of the lowest dosage of phenobarbital that can produce drug discrimination in rats. Gordon, MK; Overton, DA; Patel, BN; Pragada, SR; Stanwood, GD, 2009)	0.63
"The correlation between phenobarbitone clearance and body weight found may allow dosage adjustment to be made to achieve target steady-state plasma concentrations."	( Determination of phenobarbitone population clearance values for physically and mentally handicapped Chinese children with epilepsy. Chan, E; Chan, K; Teoh, R, )	0.13
" After withdrawal of the EP1 receptor antagonist, a low dose of the P-glycoprotein substrate phenobarbital resulted in an anticonvulsant effect in this pretreated group, whereas the same dosage of phenobarbital did not exert a significant effect in the respective control group."	( Targeting prostaglandin E2 EP1 receptors prevents seizure-associated P-glycoprotein up-regulation. Bauer, B; Gorter, JA; Hartz, AM; Pekcec, A; Potschka, H; Schlichtiger, J; Soerensen, J; Unkrüer, B; van Vliet, EA, 2009)	0.57
" Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3s stimulus duration) delivered via ocular electrodes and isobolographic analysis for parallel and non-parallel dose-response effects was used to characterize the consequent anticonvulsant interactions between the various drug combinations."	( Isobolographic characterization of interactions of levetiracetam with the various antiepileptic drugs in the mouse 6 Hz psychomotor seizure model. Luszczki, JJ; Patsalos, PN; Wlaz, A; Wojda, E, 2009)	0.35
" Blood was collected on Days 8 and 14 after each day's dosing to perform blood coagulation examination."	( Changes in blood coagulation-related parameters in phenobarbital-treated rabbits. Abe, H; Asano, Y; Edamoto, H; Fujita, M; Mochizuki, M; Okazaki, E; Saito, T; Wakabayashi, K; Yoshinaga, H, 2009)	0.6
"In the present study, NMR-based urinary metabonomic profiles resulting from dosing with widely recognized microsomal enzyme inducers were evaluated in male rats."	( Modulation of ascorbic acid metabolism by cytochrome P450 induction revealed by metabonomics and transcriptional profiling. Aranibar, N; Bhaskaran, V; Gong, L; Lecureux, L; Lehman-McKeeman, L; Nelson, D; Ott, KH; Stryker, S; Vassallo, J, 2009)	0.35
" He had received therapeutic dosing of phenobarbital and midazolam up to 5 hours prior to a brain death examination."	( A 10-month-old infant with reversible findings of brain death. deCaen, AR; Duff, J; Joffe, AR; Kolski, H, 2009)	0.62
" Nine patients received 20 mg/kg; the maximum total dosage administered was 80 mg/kg with a concentration of 283 micromol/L."	( Rescue therapy with high-dose oral phenobarbitone loading for refractory status epilepticus. Ackermann, S; Blockman, M; Karlsson, MO; van der Walt, JS; Wilmshurst, JM, 2010)	0.36
" The dosage and time of phenobarbital induction were critical for the enhanced production of ganoderic acids."	( Enhanced biosynthetic gene expressions and production of ganoderic acids in static liquid culture of Ganoderma lucidum under phenobarbital induction. Gu, T; Li, YB; Liang, CX; Miao, XL; Tang, YJ; Wang, JL; Xu, JW; Zhong, JJ, 2010)	0.87
" Based on pharmacokinetic studies with bumetanide, which showed extremely rapid elimination and low brain penetration of this drug in rats, bumetanide was administered systemically with different dosing protocols, including continuous intravenous infusion."	( Disease-modifying effects of phenobarbital and the NKCC1 inhibitor bumetanide in the pilocarpine model of temporal lobe epilepsy. Brandt, C; Heuchert, N; Löscher, W; Nozadze, M; Rattka, M, 2010)	0.65
" Thirteen patients received PB rectally or orally at a dosage of 20-30mg/kg/day initially, and the PB dosage was gradually reduced to a maintenance dosage of 5-10mg/kg/day orally."	( Effectiveness and safety of non-intravenous high-dose phenobarbital therapy for intractable epilepsy during childhood. Hamano, S; Ida, H; Kikuchi, K; Koichihara, R; Minamitani, M; Oritsu, T; Tanaka, M, 2011)	0.62
"The derived models describe well VPA clearance in terms of characteristics of Serbian pediatric and adult epileptic patients, offering a basis for rational individualization of VPA dosage regimens."	( Factors influencing valproate pharmacokinetics in children and adults. Jankovic, S; Jankovic, SM; Milovanovic, JR, 2010)	0.36
" Therefore, we had to limit the dosage to 1-1."	( Add-on treatment with verapamil in pharmacoresistant canine epilepsy. Jambroszyk, M; Potschka, H; Tipold, A, 2011)	0.37
"The failure of the maximum tolerated dosage to improve seizure control in dogs with phenobarbital-resistant epilepsy argues against the suitability of verapamil add-on treatment to overcome pharmacoresistance."	( Add-on treatment with verapamil in pharmacoresistant canine epilepsy. Jambroszyk, M; Potschka, H; Tipold, A, 2011)	0.59
" Concurrent PB administration significantly alters the pharmacokinetics of LEV in the dog, indicating that dosage adjustments might be necessary when the drug is administered with PB."	( The pharmacokinetics of levetiracetam in healthy dogs concurrently receiving phenobarbital. Moore, SA; Muñana, KR; Nettifee-Osborne, JA; Papich, MG, 2011)	0.6
" To optimize the dose regimens of these inducers for use in DDI studies, their effect at various doses and dosing durations on the area under the curve (AUC) of multiple probe substrates was simulated using a population-based simulator."	( Simulation of clinical drug-drug interactions from hepatocyte CYP3A4 induction data and its potential utility in trial designs. Hayashi, M; Shou, M; Skiles, GL; Xu, Y; Zhou, Y, 2011)	0.37
" The disease occurred after one to four years of drug therapy, at dosage of 100 mg/day."	( Dupuytren's contracture as result of prolonged administration of phenobarbital. Cordova, A; Moschella, F; Tripoli, M, 2011)	0.61
" For each drug, 6 healthy male volunteers were dosed with 100 μg (14)C-labelled compound."	( Comparative pharmacokinetics between a microdose and therapeutic dose for clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen), and phenobarbital in human volunteers. Alder, J; Bjerrum, OJ; Brian Houston, J; Garner, C; Gesson, C; Grynkiewicz, G; Jochemsen, R; Lappin, G; Oosterhuis, B; Rowland, M; Shishikura, Y; Weaver, RJ, 2011)	0.57
" Although the effects of PB in blocking the surge release of luteinizing hormone (LH), inducing anovulation and prolonging the diestrous period has been well established, there is still no research describing the appearance of persistent estrous states in normal cycling rats dosed with PB."	( Hypothyroidism caused by phenobarbital affects patterns of estrous cyclicity in rats. Ishiguro, T; Kawakami, Y; Kumazawa, T; Li, Y; Matsumoto, Y; Nishitani, H; Tagawa, Y, 2011)	0.67
" We proposed a systematic classification scheme using FDA-approved drug labeling to assess the DILI potential of drugs, which yielded a benchmark dataset with 287 drugs representing a wide range of therapeutic categories and daily dosage amounts."	( FDA-approved drug labeling for the study of drug-induced liver injury. Chen, M; Fang, H; Liu, Z; Shi, Q; Tong, W; Vijay, V, 2011)	0.37
"The derived models describe well CBZ clearance in terms of Serbian pediatric and adult epileptic patient characteristics, offering a basis for rational individualization of CBZ dosage regimens."	( Factors influencing carbamazepine pharmacokinetics in children and adults: population pharmacokinetic analysis. Jankovic, SM; Milovanovic, JR, 2011)	0.37
"We developed a new model for neonate and infant dosing of phenobarbital with good predictive performance."	( Population pharmacokinetics of phenobarbital by mixed effect modelling using routine clinical pharmacokinetic data in Japanese neonates and infants: an update. Aki, H; Ikeda, H; Mimemoto, M; Suematsu, F; Takiguchi, T; Yukawa, E; Yukawa, M, 2011)	0.9
" The addition of CYP2C19 genotyping to PK models did not improve the dosing strategies in neonates and infants."	( Effects of cytochrome P450 (CYP)2C19 polymorphisms on pharmacokinetics of phenobarbital in neonates and infants with seizures. Chung, JY; Lee, C; Lee, SM; Lee, YM; Namgung, R; Park, KI; Park, MS, 2012)	0.61
" The final model shows that for commonly used dosing regimens, the population mean PG peak and trough concentrations range between 33-144 and 28-218 mg l(-1) (peak) and 19-109 and 6-112 mg l(-1) (trough) for paracetamol and phenobarbital formulations, respectively, depending on birth weight and age of the neonates."	( Developmental pharmacokinetics of propylene glycol in preterm and term neonates. Allegaert, K; Danhof, M; De Cock, RF; de Hoon, J; Knibbe, CA; Kulo, A; Verbesselt, R, 2013)	0.57
" Moreover, a VPA dose-response curve was performed on PBMC obtained from healthy controls, demonstrating an increase of acetyl-histone H3 content."	( Valproate induces epigenetic modifications in lymphomonocytes from epileptic patients. Conti, E; Difrancesco, JC; Ferrarese, C; Galimberti, G; Riva, C; Rodriguez-Menendez, V; Ruffmann, C; Tremolizzo, L, 2012)	0.38
" Mean PGB dosage was 279 mg/day."	( Effect of pregabalin add-on treatment on seizure control, quality of life, and anxiety in patients with brain tumour-related epilepsy: a pilot study. Carapella, CM; Dinapoli, L; Fabi, A; Maschio, M; Pace, A; Pompili, A; Sperati, F; Vidiri, A, 2012)	0.38
" Standard phenobarbital dosing is appropriate for the initial treatment of seizures in neonates with hypoxic ischemic encephalopathy treated with therapeutic hypothermia."	( Population pharmacokinetics of phenobarbital in infants with neonatal encephalopathy treated with therapeutic hypothermia. Barks, JD; Bhatt-Mehta, V; Dillon, CH; Ng, CM; Shellhaas, RA, 2013)	1.08
"Microemulsions (MEs) and self-emulsifying drug delivery systems (SEEDS) containing phenobarbital (Phe) were developed to improve its chemical stability, solubilizing capacity and taste-masking in oral liquid dosage forms."	( Pharmaceutical optimization of lipid-based dosage forms for the improvement of taste-masking, chemical stability and solubilizing capacity of phenobarbital. Bregni, C; Buontempo, F; Carlucci, A; Langenheim, M; Monteagudo, E; Salerno, C, 2014)	0.83
"To clarify the dose-response relationship between constitutive androstane receptor (CAR) activity and induction of cytochrome P450 2B (CYP2B) expression and hypertrophy by triazole fungicides in mouse liver, three dose levels of cyproconazole (Cypro), tebuconazole (Teb), fluconazole (Flu), and phenobarbital (PB), a typical CYP2B inducer, were administrated in diet to male wild-type (WT) and CAR-knockout (CARKO) mice for one week."	( Dose-response involvement of constitutive androstane receptor in mouse liver hypertrophy induced by triazole fungicides. Inoue, K; Irie, K; Kodama, Y; Matsuo, S; Nishikawa, A; Ozawa, S; Takahashi, M; Tamura, K; Yoshida, M, 2013)	0.57
" Mean cumulative dosage of ch was 643."	( Treatment of neonatal abstinence syndrome in preterm and term infants. Dabek, MT; Englert, S; Poeschl, J; Ruef, P, 2013)	0.39
"5 days) of multiple dosing would be required to achieve steady-state serum concentrations."	( Pharmacokinetics of phenobarbital in dogs after multiple oral administration. Houghton, NS; Nachreiner, RF; Pedersoli, WM; Ravis, WR, 1984)	0.59
" The dosage regimen should be adjusted accordingly to gain a better clinical outcome."	( Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients. Panomvana, D; Towanabut, S; Traiyawong, T, 2013)	0.6
" A low dosage of phenobarbital caused a significant increase of the generalized seizure threshold in the L-701,324 pre-treated group, whereas it did not exert a comparable effect in animals that received vehicle during the massive kindling phase."	( Pre-treatment with the NMDA receptor glycine-binding site antagonist L-701,324 improves pharmacosensitivity in a mouse kindling model. Aronica, E; Gorter, J; Potschka, H; Salvamoser, JD; Soerensen, J; van Vliet, EA; Zellinger, C, 2014)	0.74
" Current dabigatran dosing guidelines use the Cockcroft-Gault (CG) equation to gauge renal function, instead of contemporary equations including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations employing creatinine (CKD-EPI_Cr), cystatin C (CKD-EPI_Cys) and both renal biomarkers (CKD-EPI_CrCys)."	( Correlation between trough plasma dabigatran concentrations and estimates of glomerular filtration rate based on creatinine and cystatin C. Barclay, ML; Begg, EJ; Chin, PK; Jensen, BP; Patterson, DM; Roberts, RL; Wallace, MC; Wright, DF; Zhang, M, 2014)	0.4
" Chronic oral dosing can be challenging for cat owners, leading to poor compliance."	( Therapeutic serum phenobarbital concentrations obtained using chronic transdermal administration of phenobarbital in healthy cats. Barnes Heller, HL; Delamaide Gasper, JA; Robertson, M; Trepanier, LA, 2015)	0.75
"Correct dosing of drugs in patients on renal replacement therapy may need a multidisciplinary approach and guidance by therapeutic drug monitoring."	( High phenobarbital clearance during continuous renal replacement therapy: a case report and pharmacokinetic analysis. Rosenborg, S; Saraste, L; Wide, K, 2014)	0.92
"1 μg/ml) and potassium bromide (n=2; 30-36 mg/kg/d)) resulted in successful reduction of intravenous barbiturate dosage and withdrawal from artificial ventilation."	( Effect of levetiracetam in acute encephalitis with refractory, repetitive partial seizures during acute and chronic phase. Imamura, A; Maegaki, Y; Maruta, K; Matsunami, K; Narita, A; Nishimura, Y; Ohno, K; Saiki, Y; Saito, Y; Sokota, T; Sugihara, S; Tamasaki, A; Ueda, R, 2015)	0.42
"The present study aimed to establish population pharmacokinetic model for phenobarbital (PB), examining and quantifying the magnitude of PB interactions with other antiepileptic drugs concomitantly used and to demonstrate its use for individualization of PB dosing regimen in adult epileptic patients."	( Nonlinear mixed effects modelling approach in investigating phenobarbital pharmacokinetic interactions in epileptic patients. Golubović, B; Jovanović, M; Kovačević, SV; Martinović, Ž; Miljković, B; Prostran, M; Vučićević, K, 2015)	0.89
"Developed population PB model may be used in estimating individual CL/F for adult epileptic patients and could be applied for individualizing dosing regimen taking into account dose-dependent effect of concomitantly given VPA."	( Nonlinear mixed effects modelling approach in investigating phenobarbital pharmacokinetic interactions in epileptic patients. Golubović, B; Jovanović, M; Kovačević, SV; Martinović, Ž; Miljković, B; Prostran, M; Vučićević, K, 2015)	0.66
" Because seizures reappeared during tapering the dosage of PB, potassium bromide (KBr) at a daily dose of 80 mg/kg was additionally administrated."	( [A case of acute encephalitis with refractory repetitive partial seizures successfully controlled by very-high-dose phenobarbital therapy found in a boy]. Aiba, H; Okumura, Y; Watanabe, S, 2014)	0.61
" To improve on drug compliance attending physicians need to prescribe more of the relatively cheaper AED like the phenobarbitone and to optimize drug dosage before switching to another."	( A 3 year audit of adult epilepsy care in a Nigerian tertiary hospital (2011-2013). Ademiluyi, BA; Alaofin, WA; Bello, HA; Busari, K; Desalu, OO; Sanya, EO; Wahab, KW, )	0.13
" Dosage increases might be indicated when utilizing LEV as add-on treatment with phenobarbital in dogs."	( Effect of chronic administration of phenobarbital, or bromide, on pharmacokinetics of levetiracetam in dogs with epilepsy. Muñana, KR; Nettifee-Osborne, JA; Papich, MG, )	0.63
"A correct dosage for the treatment of NAS was guaranteed."	( Design of pediatric oral formulations with a low proportion of methadone or phenobarbital for the treatment of neonatal abstinence syndrome. Calpena, AC; Clares, B; Mallandrich, M; Provenza, N; Pueyo, B, 2016)	0.66
" Two or more seizures within 3 months led to an increase in drug dosage (levetiracetam: 10 mg/kg/day, phenobarbital: 1 mg/kg/day)."	( A single-blinded phenobarbital-controlled trial of levetiracetam as mono-therapy in dogs with newly diagnosed epilepsy. Berendt, M; Fredsø, N; Møller, A; Sabers, A; Toft, N, 2016)	0.99
" First, due to both pharmacokinetic variability and non-pharmacokinetic factors, the correlation between dosage and concentration is poor in neonates, but can be overcome with the use of more complex, validated dosing regimens."	( Therapeutic drug monitoring in neonates. Allegaert, K; Pauwels, S, 2016)	0.43
" This population PK model can be applied for optimizing topiramate dosage regimens in actual clinical practice."	( Factors influencing topiramate clearance in adult patients with epilepsy: A population pharmacokinetic analysis. Bae, EK; Jang, IJ; Kim, TJ; Lee, J; Lee, KJ; Lee, SK; Moon, J; Shin, D; Shin, JW; Shin, YW, 2016)	0.43
" Type I isobolographic analysis for parallel dose-response relationship curves (DRRCs) was used to analyze the 3-drug combination."	( Isobolographic Analysis of Interaction for Three-Drug Combination of Carbamazepine, Phenobarbital and Topiramate in the Mouse Maximal Electroshock-Induced Seizure Model. Luszczki, JJ, 2016)	0.66
"The aim of this review was to evaluate current literature for dosing recommendations for the use of antiepileptic medications in patients receiving renal replacement therapy (RRT)."	( Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy. Bastin, ML; Cook, AM; Oyler, DR; Smetana, KS, 2016)	0.43
" Micromedex® DRUGDEX as well as package inserts were used to obtain known pharmacokinetic properties and dosage adjustment recommendations in RRT if known."	( Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy. Bastin, ML; Cook, AM; Oyler, DR; Smetana, KS, 2016)	0.43
"Data regarding antiepileptic drug use in RRT are limited and mostly consist of case reports limiting our proposed dosing recommendations."	( Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy. Bastin, ML; Cook, AM; Oyler, DR; Smetana, KS, 2016)	0.43
"Additional studies are necessary before specific dosing recommendations can be made for most antiepileptic drugs in critically ill patients receiving RRT, specifically with newer agents."	( Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy. Bastin, ML; Cook, AM; Oyler, DR; Smetana, KS, 2016)	0.43
" The results acquired for determination of phenobarbitone in its dosage forms utilizing the proposed sensors are in good agreement with those obtained by the British Pharmacopoeial method."	( Ionophore-based potentiometric PVC membrane sensors for determination of phenobarbitone in pharmaceutical formulations. Abounassif, M; Al-Majed, A; Alrabiah, H; Mostafa, GA, 2016)	0.43
" The dosage of PB was ranked first followed by that of CBZ and finally by the VPA."	( [Therapeutic drug monitoring of three antiepileptic drugs - Back on twenty years of experience]. Badrane, N; Bencheikh, RS; Moussa, LA; Ouammi, L; Serragui, S; Tanani, DS; Zalagh, F, 2016)	0.43
"The aims of the study were to develop a population pharmacokinetic model of orally administered brivaracetam in paediatric patients and to provide dosing suggestions."	( Brivaracetam population pharmacokinetics in children with epilepsy aged 1 month to 16 years. Schoemaker, R; Stockis, A; Wade, JR, 2017)	0.46
" Simulations were performed to investigate dosing regimens."	( Brivaracetam population pharmacokinetics in children with epilepsy aged 1 month to 16 years. Schoemaker, R; Stockis, A; Wade, JR, 2017)	0.46
" Data suggest no need to change brivaracetam dosing when used concomitantly with carbamazepine, phenobarbital or valproate."	( Brivaracetam population pharmacokinetics in children with epilepsy aged 1 month to 16 years. Schoemaker, R; Stockis, A; Wade, JR, 2017)	0.67
" This external evaluation should allow confirming the proposed dosage adaptation and extending these recommendations to the entire intensive care pediatric population."	( Phenobarbital in intensive care unit pediatric population: predictive performances of population pharmacokinetic model. Blin, O; Chasseloup, E; Guilhaumou, R; Marsot, A; Michel, F; Paut, O, 2017)	1.9
" There is increasing interest in the incorporation of epigenetic and metabolic biomarkers to complement apical data; however, a number of questions, including the tissue specificity, dose-response patterns, early detection of those endpoints, and the added value need to be addressed."	( Dose-response analysis of epigenetic, metabolic, and apical endpoints after short-term exposure to experimental hepatotoxicants. Beger, RD; Chalbot, MG; Johnson, K; Kavouras, IG; Koturbash, I; LeBaron, MJ; Lin, H; Miousse, IR; Murphy, LA; Rasoulpour, RJ; Schisler, MR; Schnackenberg, LK; Sun, J; Sura, R, 2017)	0.46
" Further, daily dosing of flupirtine decreased the seizure burden over 3 days following HI-induction, and modified the natural evolution of acute seizures."	( Anticonvulsant effect of flupirtine in an animal model of neonatal hypoxic-ischemic encephalopathy. Raol, YH; Sampath, D; Valdez, R; White, AM, 2017)	0.46
"Phenobarbital is the first-line treatment of seizures in asphyxiated neonates; however, due to the high pharmacokinetic variability in this population, there is no consensus on the optimal dosage regimen."	( Estimation of initial phenobarbital dosing in term neonates with moderate-to-severe hypoxic ischaemic encephalopathy following perinatal asphyxia. Hartinger, J; Pokorná, P; Šíma, M; Slanař, O, 2018)	2.24
"This study presents basis for phenobarbital initial dosing in term asphyxiated neonates during first week of life."	( Estimation of initial phenobarbital dosing in term neonates with moderate-to-severe hypoxic ischaemic encephalopathy following perinatal asphyxia. Hartinger, J; Pokorná, P; Šíma, M; Slanař, O, 2018)	1.08
" This mechanism may be significant for the clinical dosage of patients with alcohol dependence."	( Molecular spectroscopic studies examining the interactions between phenobarbital and human serum albumin in alcohol consumption. Cui, SF; Li, W; Zhou, CH, 2018)	0.72
"In this report, we describe a human immunodeficiency virus (HIV)-infected patient in whom changes in phenobarbital (PB) dosage resulted in associated changes in plasma concentrations of dolutegravir (DTG)."	( A potential drug interaction between phenobarbital and dolutegravir: A case report. Hideta, K; Higasa, S; Hikasa, S; Kimura, T; Sawada, A; Seino, H; Shimabukuro, S; Tokugawa, T; Uwa, N, 2018)	0.97
" Rats were either fed diets containing 0 (control) or 500 ppm NaPB or were dosed with 0 (control) or 100 mg/kg/day PCN orally for 7 days."	( Comparison of the hepatic and thyroid gland effects of sodium phenobarbital in wild type and constitutive androstane receptor (CAR) knockout rats and pregnenolone-16α-carbonitrile in wild type and pregnane X receptor (PXR) knockout rats. Chatham, LR; Elcombe, CR; Foster, JR; Haines, C; Lake, BG; Vardy, A, 2018)	0.72
"Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used."	( Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry. Battino, D; Bonizzoni, E; Craig, J; Lindhout, D; Perucca, E; Sabers, A; Thomas, SV; Tomson, T; Vajda, F, 2018)	0.48
" Subsequent dosing nomograms are provided for phenobarbital dosing during ECMO."	( Phenobarbital pharmacokinetics in neonates and infants during extracorporeal membrane oxygenation. Pokorná, P; Šíma, M; Slanař, O; Tibboel, D; Vobruba, V, 2018)	2.18
" Pharmacokinetic data for this patient population is lacking and would assist in dosing decisions."	( Phenobarbital population pharmacokinetics across the pediatric age spectrum. Galati, M; Kayyal, SY; Moffett, BS; Placencia, JL; Riviello, JJ; Rodman, EA; Weingarten, MM, 2018)	1.92
"We evaluated DDIs and adjusted the dosage of drugs by monitoring the serum drug level."	( Drug-drug interactions among drugs prescribed for nontuberculous mycobacterial infection and epilepsy: A case report. Hatanaka, M; Ikeda, R; Matsumoto, N; Oda, Y; Sonoda, J; Tazaki, T; Yoshikawa, N, 2019)	0.51
" Although PG is generally considered safe, the dosage can exceed safety thresholds in neonates."	( Spectroscopic detection of brain propylene glycol in neonates: Effects of different pharmaceutical formulations of phenobarbital. Pouwels, PJW; van de Lagemaat, M; van de Pol, LA; Witjes, BCM; Zonnenberg, IA, 2019)	0.72
" Additionally, in this case the interaction was managed with concentration-guided dosing of apixaban, suggesting this approach may represent a feasible strategy for managing patients requiring treatment with direct-acting oral anticoagulants and enzyme-inducing antiepileptic drugs."	( Managing Direct Oral Anticoagulants in Patients With Antiepileptic Medication. Dagan, G; Hochberg-Klein, S; Kalish, Y; Muszkat, M; Perlman, A, 2018)	0.48
" Finally, a theoretical hemin effect was implemented to illustrate the applicability of the model to dosage optimization in drug therapies."	( Computational disease model of phenobarbital-induced acute attacks in an acute intermittent porphyria mouse model. Fontanellas, A; Jericó, D; Parra-Guillén, ZP; Sampedro, A; Serrano-Mendioroz, I; Trocóniz, IF; Vera-Yunca, D, 2019)	0.8
" Poor correlation between TD dosage and S-PB concentrations was observed and more dosage adjustments were required during TD administration."	( Prospective crossover clinical trial comparing transdermal with oral phenobarbital administration in epileptic cats. Barnes Heller, HL; Mei, C; Robertson, M; Trepanier, LA, 2019)	0.75
"Determination of phenobarbital (PB) dosing during continuous haemodiafiltration (CHDF) requires evaluation of both the patient's own clearance and CHDF clearance."	( Successful treatment of seizure disorder by evaluating phenobarbital clearance in a paediatric patient undergoing continuous haemodiafiltration. Ishii, I; Suzuki, T; Takatsuka, H; Yamazaki, S, 2019)	1.1
" Dosage adjustment produced seizure control."	( Successful treatment of seizure disorder by evaluating phenobarbital clearance in a paediatric patient undergoing continuous haemodiafiltration. Ishii, I; Suzuki, T; Takatsuka, H; Yamazaki, S, 2019)	0.76
" Nonresponse was defined as continued seizures after maximum dosing of phenobarbital or an additional antiepileptic."	( Clinical, Neuroimaging, and Electrographic Predictors of Phenobarbital Failure in Newborns With Hypoxic Ischemic Encephalopathy and Seizures. Dwivedi, D; Holland, K; Kline-Fath, B; Lin, N; Schapiro, M; Venkatesan, C, 2019)	0.99
"To assess pharmacokinetics and clinical anti-epileptic effectiveness of phenobarbital and midazolam in asphyxiated neonates and to develop dosing guidelines."	( Phenobarbital, Midazolam Pharmacokinetics, Effectiveness, and Drug-Drug Interaction in Asphyxiated Neonates Undergoing Therapeutic Hypothermia. Cools, F; de Haan, TR; Dijk, PH; Dijkman, KP; Egberts, TCG; Favié, LMA; Groenendaal, F; Huitema, ADR; Nuytemans, DHGM; Rademaker, CMA; Rijken, M; Simons, SHP; van Bel, F; van den Broek, MPH; van der Lee, JH; van Heijst, A; van Straaten, HLM; Zecic, A; Zonnenberg, IA, 2019)	2.19
" These preliminary results suggest that oral administration of multiple doses of PB increases the required CsA dosage in CsA-based immunosuppressive therapy in cats."	( Interaction of cyclosporine with phenobarbital in cats: a preliminary study. Fukui, D; Hoshino, Y; Inden, T; Katayama, M; Otaka, R; Satoh, H, 2019)	0.8
"To develop a population pharmacokinetic model for IV phenobarbital in neonates following cardiac surgery and perform simulations to identify optimal dosing regimens."	( Population Pharmacokinetics of IV Phenobarbital in Neonates After Congenital Heart Surgery. Abend, NS; Massey, SL; Naim, MY; Thibault, C; Zuppa, AF, 2020)	1.09
" Logistic regression analyses revealed significant associations between adverse effect occurrence and both phenobarbitone starting dosage and administration of a second antiepileptic drug (AED)."	( Prevalence and clinical characteristics of phenobarbitone-associated adverse effects in epileptic cats. Corsini, G; De Risio, L; Gutierrez-Quintana, R; Marsh, O; Van Dijk, J, 2021)	0.62
" Increased phenobarbitone starting dosage and the addition of a second AED were significantly associated with the occurrence of adverse effects."	( Prevalence and clinical characteristics of phenobarbitone-associated adverse effects in epileptic cats. Corsini, G; De Risio, L; Gutierrez-Quintana, R; Marsh, O; Van Dijk, J, 2021)	0.62
"Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634)."	( Abbasi, S; Abd El-Wahab, A; Abdallah, M; Abebe, G; Aca-Aca, G; Adama, S; Adefegha, SA; Adidigue-Ndiome, R; Adiseshaiah, P; Adrario, E; Aghajanian, C; Agnese, W; Ahmad, A; Ahmad, I; Ahmed, MFE; Akcay, OF; Akinmoladun, AC; Akutagawa, T; Alakavuklar, MA; Álava-Rabasa, S; Albaladejo-Florín, MJ; Alexandra, AJE; Alfawares, R; Alferiev, IS; Alghamdi, HS; Ali, I; Allard, B; Allen, JD; Almada, E; Alobaid, A; Alonso, GL; Alqahtani, YS; Alqarawi, W; Alsaleh, H; Alyami, BA; Amaral, BPD; Amaro, JT; Amin, SAW; Amodio, E; Amoo, ZA; Andia Biraro, I; Angiolella, L; Anheyer, D; Anlay, DZ; Annex, BH; Antonio-Aguirre, B; Apple, S; Arbuznikov, AV; Arinsoy, T; Armstrong, DK; Ash, S; Aslam, M; Asrie, F; Astur, DC; Atzrodt, J; Au, DW; Aucoin, M; Auerbach, EJ; Azarian, S; Ba, D; Bai, Z; Baisch, PRM; Balkissou, AD; Baltzopoulos, V; Banaszewski, M; Banerjee, S; Bao, Y; Baradwan, A; Barandika, JF; Barger, PM; Barion, MRL; Barrett, CD; Basudan, AM; Baur, LE; Baz-Rodríguez, SA; Beamer, P; Beaulant, A; Becker, DF; Beckers, C; Bedel, J; Bedlack, R; Bermúdez de Castro, JM; Berry, JD; Berthier, C; Bhattacharya, D; Biadgo, B; Bianco, G; Bianco, M; Bibi, S; Bigliardi, AP; Billheimer, D; Birnie, DH; Biswas, K; Blair, HC; Bognetti, P; Bolan, PJ; Bolla, JR; Bolze, A; Bonnaillie, P; Borlimi, R; Bórquez, J; Bottari, NB; Boulleys-Nana, JR; Brighetti, G; Brodeur, GM; Budnyak, T; Budnyk, S; Bukirwa, VD; Bulman, DM; Burm, R; Busman-Sahay, K; Butcher, TW; Cai, C; Cai, H; Cai, L; Cairati, M; Calvano, CD; Camacho-Ordóñez, A; Camela, E; Cameron, T; Campbell, BS; Cansian, RL; Cao, Y; Caporale, AS; Carciofi, AC; Cardozo, V; Carè, J; Carlos, AF; Carozza, R; Carroll, CJW; Carsetti, A; Carubelli, V; Casarotta, E; Casas, M; Caselli, G; Castillo-Lora, J; Cataldi, TRI; Cavalcante, ELB; Cavaleiro, A; Cayci, Z; Cebrián-Tarancón, C; Cedrone, E; Cella, D; Cereda, C; Ceretti, A; Ceroni, M; Cha, YH; Chai, X; Chang, EF; Chang, TS; Chanteux, H; Chao, M; Chaplin, BP; Chaturvedi, S; Chaturvedi, V; Chaudhary, DK; Chen, A; Chen, C; Chen, HY; Chen, J; Chen, JJ; Chen, K; Chen, L; Chen, Q; Chen, R; Chen, SY; Chen, TY; Chen, WM; Chen, X; Chen, Y; Cheng, G; Cheng, GJ; Cheng, J; Cheng, YH; Cheon, HG; Chew, KW; Chhoker, S; Chiu, WN; Choi, ES; Choi, MJ; Choi, SD; Chokshi, S; Chorny, M; Chu, KI; Chu, WJ; Church, AL; Cirrincione, A; Clamp, AR; Cleff, MB; Cohen, M; Coleman, RL; Collins, SL; Colombo, N; Conduit, N; Cong, WL; Connelly, MA; Connor, J; Cooley, K; Correa Ramos Leal, I; Cose, S; Costantino, C; Cottrell, M; Cui, L; Cundall, J; Cutaia, C; Cutler, CW; Cuypers, ML; da Silva Júnior, FMR; Dahal, RH; Damiani, E; Damtie, D; Dan-Li, W; Dang, Z; Dasa, SSK; Davin, A; Davis, DR; de Andrade, CM; de Jong, PL; de Oliveira, D; de Paula Dorigam, JC; Dean, A; Deepa, M; Delatour, C; Dell'Aiera, S; Delley, MF; den Boer, RB; Deng, L; Deng, Q; Depner, RM; Derdau, V; Derici, U; DeSantis, AJ; Desmarini, D; Diffo-Sonkoue, L; Divizia, M; Djenabou, A; Djordjevic, JT; Dobrovolskaia, MA; Domizi, R; Donati, A; Dong, Y; Dos Santos, M; Dos Santos, MP; Douglas, RG; Duarte, PF; Dullaart, RPF; Duscha, BD; Edwards, LA; Edwards, TE; Eichenwald, EC; El-Baba, TJ; Elashiry, M; Elashiry, MM; Elashry, SH; Elliott, A; Elsayed, R; Emerson, MS; Emmanuel, YO; Emory, TH; Endale-Mangamba, LM; Enten, GA; Estefanía-Fernández, K; Estes, JD; Estrada-Mena, FJ; Evans, S; Ezra, L; Faria de, RO; Farraj, AK; Favre, C; Feng, B; Feng, J; Feng, L; Feng, W; Feng, X; Feng, Z; Fernandes, CLF; Fernández-Cuadros, ME; Fernie, AR; Ferrari, D; Florindo, PR; Fong, PC; Fontes, EPB; Fontinha, D; Fornari, VJ; Fox, NP; Fu, Q; Fujitaka, Y; Fukuhara, K; Fumeaux, T; Fuqua, C; Fustinoni, S; Gabbanelli, V; Gaikwad, S; Gall, ET; Galli, A; Gancedo, MA; Gandhi, MM; Gao, D; Gao, K; Gao, M; Gao, Q; Gao, X; Gao, Y; Gaponenko, V; Garber, A; Garcia, EM; García-Campos, C; García-Donas, J; García-Pérez, AL; Gasparri, F; Ge, C; Ge, D; Ge, JB; Ge, X; George, I; George, LA; Germani, G; Ghassemi Tabrizi, S; Gibon, Y; Gillent, E; Gillies, RS; Gilmour, MI; Goble, S; Goh, JC; Goiri, F; Goldfinger, LE; 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Shen, BQ; Shen, CH; Shen, P; Shen, S; Shen, Y; Shen, Z; Shi, J; Shi-Li, L; Shimoda, K; Shoji, Y; Shun, C; Silva, MA; Silva-Cardoso, J; Simas, NK; Simirgiotis, MJ; Sincock, SA; Singh, MP; Sionis, A; Siu, J; Sivieri, EM; Sjerps, MJ; Skoczen, SL; Slabon, A; Slette, IJ; Smith, MD; Smith, S; Smith, TG; Snapp, KS; Snow, SJ; Soares, MCF; Soberman, D; Solares, MD; Soliman, I; Song, J; Sorooshian, A; Sorrell, TC; Spinar, J; Staudt, A; Steinhart, C; Stern, ST; Stevens, DM; Stiers, KM; Stimming, U; Su, YG; Subbian, V; Suga, H; Sukhija-Cohen, A; Suksamrarn, A; Suksen, K; Sun, J; Sun, M; Sun, P; Sun, W; Sun, XF; Sun, Y; Sundell, J; Susan, LF; Sutjarit, N; Swamy, KV; Swisher, EM; Sykes, C; Takahashi, JA; Talmor, DS; Tan, B; Tan, ZK; Tang, L; Tang, S; Tanner, JJ; Tanwar, M; Tarazi, Z; Tarvasmäki, T; Tay, FR; Teketel, A; Temitayo, GI; Thersleff, T; Thiessen Philbrook, H; Thompson, LC; Thongon, N; Tian, B; Tian, F; Tian, Q; Timothy, AT; Tingle, MD; Titze, IR; Tolppanen, H; Tong, W; Toyoda, H; Tronconi, L; Tseng, CH; Tu, H; Tu, YJ; Tung, SY; Turpault, S; Tuynman, JB; Uemoto, AT; Ugurlu, M; Ullah, S; Underwood, RS; Ungell, AL; Usandizaga-Elio, I; Vakonakis, I; van Boxel, GI; van den Beucken, JJJP; van der Boom, T; van Slegtenhorst, MA; Vanni, JR; Vaquera, A; Vasconcellos, RS; Velayos, M; Vena, R; Ventura, G; Verso, MG; Vincent, RP; Vitale, F; Vitali, S; Vlek, SL; Vleugels, MPH; Volkmann, N; Vukelic, M; Wagner Mackenzie, B; Wairagala, P; Waller, SB; Wan, J; Wan, MT; Wan, Y; Wang, CC; Wang, H; Wang, J; Wang, JF; Wang, K; Wang, L; Wang, M; Wang, S; Wang, WM; Wang, X; Wang, Y; Wang, YD; Wang, YF; Wang, Z; Wang, ZG; Warriner, K; Weberpals, JI; Weerachayaphorn, J; Wehrli, FW; Wei, J; Wei, KL; Weinheimer, CJ; Weisbord, SD; Wen, S; Wendel Garcia, PD; Williams, JW; Williams, R; Winkler, C; Wirman, AP; Wong, S; Woods, CM; Wu, B; Wu, C; Wu, F; Wu, P; Wu, S; Wu, Y; Wu, YN; Wu, ZH; Wurtzel, JGT; Xia, L; Xia, Z; Xia, ZZ; Xiao, H; Xie, C; Xin, ZM; Xing, Y; Xing, Z; Xu, S; Xu, SB; Xu, T; Xu, X; Xu, Y; Xue, L; Xun, J; Yaffe, MB; Yalew, A; Yamamoto, S; Yan, D; Yan, H; Yan, S; Yan, X; Yang, AD; Yang, E; Yang, H; Yang, J; Yang, JL; Yang, K; Yang, M; Yang, P; Yang, Q; Yang, S; Yang, W; Yang, X; Yang, Y; Yao, JC; Yao, WL; Yao, Y; Yaqub, TB; Ye, J; Ye, W; Yen, CW; Yeter, HH; Yin, C; Yip, V; Yong-Yi, J; Yu, HJ; Yu, MF; Yu, S; Yu, W; Yu, WW; Yu, X; Yuan, P; Yuan, Q; Yue, XY; Zaia, AA; Zakhary, SY; Zalwango, F; Zamalloa, A; Zamparo, P; Zampini, IC; Zani, JL; Zeitoun, R; Zeng, N; Zenteno, JC; Zepeda-Palacio, C; Zhai, C; Zhang, B; Zhang, G; Zhang, J; Zhang, K; Zhang, Q; Zhang, R; Zhang, T; Zhang, X; Zhang, Y; Zhang, YY; Zhao, B; Zhao, D; Zhao, G; Zhao, H; Zhao, Q; Zhao, R; Zhao, S; Zhao, T; Zhao, X; Zhao, XA; Zhao, Y; Zhao, Z; Zheng, Z; Zhi-Min, G; Zhou, CL; Zhou, HD; Zhou, J; Zhou, W; Zhou, XQ; Zhou, Z; Zhu, C; Zhu, H; Zhu, L; Zhu, Y; Zitzmann, N; Zou, L; Zou, Y, 2022)	0.72
"To identify factors associated with low benzodiazepine (BZD) dosing in patients with refractory status epilepticus (RSE) and to assess the impact of BZD treatment variability on seizure cessation."	( First-line medication dosing in pediatric refractory status epilepticus. Abend, NS; Amengual-Gual, M; Anderson, A; Arya, R; Brenton, JN; Carpenter, JL; Chapman, K; Clark, J; Farias-Moeller, R; Gaillard, WD; Gaínza-Lein, M; Glauser, T; Goldstein, JL; Goodkin, HP; Guerriero, RM; Kapur, K; Lai, YC; Loddenkemper, T; McDonough, TL; Mikati, MA; Morgan, LA; Novotny, EJ; Ostendorf, AP; Payne, ET; Peariso, K; Piantino, J; Riviello, JJ; Sannagowdara, K; Tasker, RC; Tchapyjnikov, D; Topjian, A; Vasquez, A; Wainwright, MS; Wilfong, A; Williams, K, 2020)	0.56
" We used logistic regression modeling to evaluate predictors of low BZD dosing and multivariate Cox regression analysis to assess the impact of low BZD dosing on time to seizure cessation."	( First-line medication dosing in pediatric refractory status epilepticus. Abend, NS; Amengual-Gual, M; Anderson, A; Arya, R; Brenton, JN; Carpenter, JL; Chapman, K; Clark, J; Farias-Moeller, R; Gaillard, WD; Gaínza-Lein, M; Glauser, T; Goldstein, JL; Goodkin, HP; Guerriero, RM; Kapur, K; Lai, YC; Loddenkemper, T; McDonough, TL; Mikati, MA; Morgan, LA; Novotny, EJ; Ostendorf, AP; Payne, ET; Peariso, K; Piantino, J; Riviello, JJ; Sannagowdara, K; Tasker, RC; Tchapyjnikov, D; Topjian, A; Vasquez, A; Wainwright, MS; Wilfong, A; Williams, K, 2020)	0.56
" Low total BZD dosing was associated with decreased likelihood of Seizure cessation."	( First-line medication dosing in pediatric refractory status epilepticus. Abend, NS; Amengual-Gual, M; Anderson, A; Arya, R; Brenton, JN; Carpenter, JL; Chapman, K; Clark, J; Farias-Moeller, R; Gaillard, WD; Gaínza-Lein, M; Glauser, T; Goldstein, JL; Goodkin, HP; Guerriero, RM; Kapur, K; Lai, YC; Loddenkemper, T; McDonough, TL; Mikati, MA; Morgan, LA; Novotny, EJ; Ostendorf, AP; Payne, ET; Peariso, K; Piantino, J; Riviello, JJ; Sannagowdara, K; Tasker, RC; Tchapyjnikov, D; Topjian, A; Vasquez, A; Wainwright, MS; Wilfong, A; Williams, K, 2020)	0.56
"The objective of this study was to describe the pharmacokinetics (PK) of intravenous phenobarbital in neonates and infants on extracorporeal membrane oxygenation (ECMO) and to provide dosing recommendations in this population."	( Population Pharmacokinetics of Phenobarbital in Neonates and Infants on Extracorporeal Membrane Oxygenation and the Influence of Concomitant Renal Replacement Therapy. Abend, NS; Massey, SL; Naim, MY; Thibault, C; Zoraian, A; Zuppa, AF, 2021)	1.13
" All dosing regimens were maintained for 7 days."	( Drug-drug interaction comparison between tacrolimus and phenobarbital in different formulations for paediatrics and adults. Chen, J; Liu, W; Lu, X; Wang, N; Zhang, Y; Zhao, X; Zhu, L; Zuo, M, 2021)	0.87
" Similar dose-related responses were seen following the week-long dosing protocol for carbamazepine, phenobarbital, and phenytoin, and these responses were associated with drug levels that were in the human therapeutic range."	( Chronic limbic epilepsy models for therapy discovery: Protocols to improve efficiency. Bertram, EH; Edelbroek, P, 2021)	0.84
"Two chromatographic methods have been proposed for the simultaneous determination of acefylline piperazine (ACEF) and phenobarbital (PHENO) in presence of methylparaben as additive in pharmaceutical dosage form."	( Validated Smart Different Chromatographic Methods for Selective Quantification of Acefylline Piperazine, Phenobarbital Sodium and Methylparaben Additive in Bulk and Pharmaceutical Dosage Form. Algmaal, SE; Boltia, SA; El Saharty, YS; Mostafa, NM, 2022)	1.14
" The purpose of this study was to compare the incidence of mechanical ventilation in patients with benzodiazepine-resistant alcohol withdrawal between front-loaded and low-intermittent phenobarbital dosing strategies."	( Front-Loaded Versus Low-Intermittent Phenobarbital Dosing for Benzodiazepine-Resistant Severe Alcohol Withdrawal Syndrome. Dodd, KW; Hanif, T; Rachid, M; Shah, P; Stegner-Smith, KL, 2022)	1.19
" The incidence of mechanical ventilation was 13 (28%) in the front-loaded dosing group vs."	( Front-Loaded Versus Low-Intermittent Phenobarbital Dosing for Benzodiazepine-Resistant Severe Alcohol Withdrawal Syndrome. Dodd, KW; Hanif, T; Rachid, M; Shah, P; Stegner-Smith, KL, 2022)	0.99
" With the current recommended dosage for phenobarbitone (40 mg/kg), we have noticed that babies are drowsier and their blood levels of phenobarbitone are more than the normal expected range."	( Comparing the effect of different loading doses of phenobarbitone on serum phenobarbitone levels in babies with neonatal seizures and effect of therapeutic hypothermia on phenobarbitone levels. Kumar, M; Palaparthy, V; Rebekah, G; Thomas, N, 2022)	0.72
" This highlights the need for prospective trials to establish an evidence base for therapeutic approaches, including validated measures of withdrawal severity and more information relating to the safe and effective dosing of phenobarbital."	( Phenobarbital to manage severe gamma-hydroxybutyrate withdrawal: A case series. Brett, J; Ezard, N; Freeman, G; Nic Ionmhain, U; Ramanathan, J; Roberts, DM; Rodgers, C; Siefried, KJ, 2023)	2.54
" This paper presents the data of the study where 6-propylthiouracil (6-PTU, 10 ppm) and sodium phenobarbital (NaPB, 1000 ppm) were dosed by feeding from gestational days (GD)6-20, and from GD6 to lactation day 21."	( Feasibility study for a downsized comparative thyroid assay with measurement of brain thyroid hormones and histopathology in rats: Case study with 6-propylthiouracil and sodium phenobarbital at high dose. Aoyama, H; Fukuda, T; Hojo, H; Iwashita, K; Kosaka, T; Minami, K; Ogata, K; Sato, A; Suto, H; Takahashi, N; Tomiyama, N; Yamada, T, 2023)	1.32
" Further research is needed to identify an optimal dosing strategy for TSCU patients at high risk for severe AWS."	( Phenobarbital for the Management of Alcohol Withdrawal Syndrome in Critically Ill, Surgical-Trauma Patients. Chau, T; Chuang, L; Goldenberg-Sandau, A; Igneri, L; Pham, C; Sensenig, R; Solomon, D, 2023)	2.35
" Six studies done in the general floors or ICUs compared PB and BZD monotherapy, while four compared the utility of adjunct PB in addition to BZD compared with BZD monotherapy and one was a database study without specific dosing information."	( Current evidence and clinical utility of phenobarbital for alcohol withdrawal syndrome. Choi, H; Colgan, B; Kistler, H; Mercado, F; Nishimura, Y, 2023)	1.18
" Future prospective studies or trials should focus on the standardization of PB dosing and outcomes."	( Current evidence and clinical utility of phenobarbital for alcohol withdrawal syndrome. Choi, H; Colgan, B; Kistler, H; Mercado, F; Nishimura, Y, 2023)	1.18
" Success of treatment correlated with higher dosing and serum levels."	( Phenobarbital in super-refractory status epilepticus (PIRATE): A retrospective, multicenter analysis. Dimitriadis, K; Kunst, S; Madlener, M; Madžar, D; Malter, M; Meyer, L; Minnerup, J; Mueller, A; Neumann, B; Pelz, JO; Reindl, C; Rojo, M; Schmidbauer, ML, 2023)	2.35
"97%), switching to or adjusting carbamazepine dosage (27."	( The impact of a newly established specialized pediatric epilepsy center in Tanzania: An observational study. Aricò, M; Di Noia, SP; Kalolo, A; Mabusi, MS; Mastrangelo, M; Pisani, F, 2023)	0.91