Page last updated: 2024-10-15

pyrimidinones

Description

Pyrimidinones: Heterocyclic compounds known as 2-pyrimidones (or 2-hydroxypyrimidines) and 4-pyrimidones (or 4-hydroxypyrimidines) with the general formula C4H4N2O. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID162786624
MeSH IDM0018261

Synonyms (4)

Synonym
pyrimidinones
1335-05-3
unii-40ygl76fc7
40ygl76fc7 ,

Toxicity

ExcerptReference
"The LD50 of sulfluramid topically applied to 2-d-old, fifth instars of the German cockroach, Blattella germanica (L."( Topical and oral toxicity of sulfluramid, a delayed-action insecticide, against the German cockroach (Dictyoptera: Blattellidae).
Barcay, SJ; Bennett, GW; Reid, BL, 1990
)
" Both substances were found to be more toxic against neuroblastoma cells than against hematopoietic stem cells."( Cytotoxic effects of 6-hydroxydopamine, merocyanine-540 and related compounds on human neuroblastoma and hematopoietic stem cells.
Bruchelt, G; Esterbauer, H; Grygar, G; Niethammer, D; Treuner, J, 1989
)
" At toxic concentrations, two of the least potent analogs, SK&F 92909 and SK&F 9205A both caused a rapid decrease in hepatocyte O2 consumption and ATP content which occurred before any evidence of cell injury."( Toxicity of H2-receptor antagonists to isolated rat hepatocytes: structure-activity relationships.
Alberts, D; Brown, TH; Durant, GJ; Lupo, S; Rush, GF; Yodis, LA, 1988
)
" administration, the lethal dose and the LD50 dose were 240 and 160 mg/kg, respectively."( Biodistribution and toxicity of photoproducts of merocyanine 540.
Battaglino, M; Gulliya, KS; Matthews, JL; Pervaiz, S, 1993
)
" The participation of some cytochrome P-450 isozymes, induced by MC and DEX, in biotransformation of MP to more toxic product(s) was suggested."( Toxicity and enzyme-inducing effect of the antiviral compound mopyridone in mice.
Rangelova, DS; Tantcheva, LP, 1996
)
" Three patients discontinued therapy for drug-related adverse events."( Safety and antiviral activity at 48 weeks of lopinavir/ritonavir plus nevirapine and 2 nucleoside reverse-transcriptase inhibitors in human immunodeficiency virus type 1-infected protease inhibitor-experienced patients.
Benson, CA; Brun, SC; Deeks, SG; Eron, JJ; Feinberg, J; Gulick, RM; Hicks, C; Hsu, A; Japour, AJ; Kempf, D; Kessler, HA; King, M; Murphy, RL; Real, K; Riddler, S; Sax, PE; Stryker, R; Sun, E; Thompson, M; Wheeler, D, 2002
)
" The cytotoxicity of these derivatives was selection with no apparent toxic effect toward normal fibroblasts."( Synthesis and in vitro cytotoxicity of 5-substituted 2-cyanoimino-4-imidazodinone and 2-cyanoimino-4-pyrimidinone derivatives.
Chang, CM; Chang, CS; Chern, JH; Lee, CC; Lee, YC; Lin, YT; Shia, KS; Tai, CL; Tseng, HY, 2004
)
" In our clinical setting IDV/r showed to be less effective and more toxic than LPV/RTV as first-line HAART."( Lopinavir/ritonavir vs. indinavir/ritonavir in antiretroviral naive HIV-infected patients: immunovirological outcome and side effects.
Adorni, F; Bini, T; Bongiovanni, M; Chiesa, E; Cicconi, P; Monforte d'Arminio, A, 2004
)
" Discontinuation due to adverse events is infrequent."( Safety, efficacy and development of resistance under the new protease inhibitor lopinavir/ritonavir: 48-week results.
Kaiser, R; Mauss, S; Rockstroh, JK; Schmutz, G; Vogel, M; Voigt, E; Wasmuth, JC, 2004
)
" Twenty-eight patients discontinued therapy prior to week 204 because of adverse events (n = 10), lost to follow-up (n = 9), or other reasons (n = 9)."( Long-term safety and durable antiretroviral activity of lopinavir/ritonavir in treatment-naive patients: 4 year follow-up study.
Benson, C; Brun, SC; Eron, JJ; Gulick, RM; Hicks, C; Kessler, HA; King, KR; King, MS; Murphy, RL; White, AC, 2004
)
" Both regimens were well tolerated with no differences in adverse events were observed."( A comparative trial of the safety and efficacy of 0.1 percent pemirolast potassium ophthalmic solution dosed twice or four times a day in patients with seasonal allergic conjunctivitis.
Gous, P; Ropo, A, 2004
)
"Liver toxicity is a common side effect of antiretroviral therapy, particularly in subjects coinfected with the hepatitis C virus (HCV)."( Short communication: liver toxicity of lopinavir-containing regimens in HIV-infected patients with or without hepatitis C coinfection.
González-Lahoz, J; González-Requena, D; Jiménez-Nacher, I; Núñez, M; Soriano, V, 2004
)
" These data have now provided a clear and clinically relevant understanding of the individual profiles of drugs within the nucleoside analogue reverse transcriptase inhibitor , HIV protease inhibitor and non-nucleoside analogue reverse transcriptase inhibitor drug classes, and have provided a rational basis for assessing and monitoring these adverse effects in clinical practice."( Adverse effects of antiretroviral therapy for HIV infection: a review of selected topics.
Mallal, S; Nolan, D; Reiss, P, 2005
)
" Parameters studied were HIV RNA, CD4+ cell counts, metabolic parameters and drug-related adverse events."( Predictive factors of lopinavir/ritonavir discontinuation for drug-related toxicity: results from a cohort of 416 multi-experienced HIV-infected individuals.
Bini, T; Bongiovanni, M; Chiesa, E; Cicconi, P; Di Biagio, A; Landonio, S; Meraviglia, P; Monforte, Ad; Testa, L; Tordato, F, 2005
)
"The SCOLTA project (Surveillance Cohort Long-term Toxicity Antiretrovirals) is a system for online surveying of adverse reactions to recently commercialized antiretroviral drugs and a "sentinel" for unexpected and late adverse reactions arising during any antiretroviral treatment (available at: http://www."( An Italian approach to postmarketing monitoring: preliminary results from the SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals) project on the safety of lopinavir/ritonavir.
Armignacco, O; Bonfanti, P; Carradori, S; Magnani, C; Martinelli, C; Parruti, G; Quirino, T; Ricci, E, 2005
)
" Adverse events were described in 18 children."( Safety and antiviral response at 12 months of lopinavir/ritonavir therapy in human immunodeficiency virus-1-infected children experienced with three classes of antiretrovirals.
Cabrero, E; De José, MI; Dueñas, J; Fortuny, C; González-Montero, R; Mellado, MJ; Muñoz-Fernández, MA; Mur, A; Navarro, M; Otero, C; Pocheville, I; Ramos, JT, 2005
)
" Treatment was not discontinued in any patient because of adverse effects."( Atazanavir and lopinavir/ritonavir: pharmacokinetics, safety and efficacy of a promising double-boosted protease inhibitor regimen.
Azuaje, C; Crespo, M; Curran, A; Diaz, M; Feijoo, M; Lopez, RM; Ocaña, I; Pahissa, A; Pou, L; Ribera, E, 2006
)
" Subsequently, the patient developed a possible adverse skin reaction to his antiretrovirals and was hospitalized."( Carbamazepine toxicity induced by lopinavir/ritonavir and nelfinavir.
Bates, DE; Herman, RJ, 2006
)
" Telbivudine was well tolerated in the studied dose range in healthy Chinese subjects, with no pattern of dose-related clinical or laboratory adverse events."( Single-dose and multiple-dose pharmacokinetics and safety of telbivudine after oral administration in healthy Chinese subjects.
Brown, NA; Chao, GC; Hu, P; Jiang, J; Pietropaolo, K; Wang, H; Zhou, XJ, 2006
)
" Together, these in vitro results indicate that combination with other antiretrovirals does not significantly increase the toxic potential of TFV in RPTECs."( In vitro cytotoxicity and mitochondrial toxicity of tenofovir alone and in combination with other antiretrovirals in human renal proximal tubule cells.
Alvarez, ML; Cihlar, T; Cordobilla, B; Domingo, JC; Domingo, P; Giralt, M; Guallar, J; López-Dupla, M; Sánchez de la Rosa, R; Saumoy, M; Torres, F; Vidal, F; Villarroya, F, 2006
)
" Safety data were generally similar between the groups; grade 3 or 4 adverse events occurred in 80 (27%) darunavir-ritonavir and 89 (30%) lopinavir-ritonavir patients."( Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial.
Banhegyi, D; Berger, D; de Béthune, MP; De Pauw, M; Lefebvre, E; Madruga, JV; McMurchie, M; Norris, D; Ruxrungtham, K; Spinosa-Guzman, S; Suter, F; Tomaka, F; Vangeneugden, T, 2007
)
" No statistically significant differences in adverse event incidence occurred between treatment groups, except for a higher vomiting rate in the 400/300 mg dose group."( High-dose lopinavir/ritonavir in highly treatment-experienced HIV-1 patients: efficacy, safety, and predictors of response.
Bernstein, B; Brun, SC; Eron, JJ; Flexner, C; Havlir, DV; Katlama, C; King, MS; Klein, CE; Letendre, SL; Podzamczer, D,
)
" A saquinavir C(min) > 2000 ng/ml was associated with an increased risk of gastrointestinal grade 3 or 4 adverse events and higher total cholesterol."( Pharmacokinetics of two randomized trials evaluating the safety and efficacy of indinavir, saquinavir and lopinavir in combination with low-dose ritonavir: the MaxCmin1 and 2 trials.
Cahn, P; Castagna, A; Clumeck, N; Dragsted, UB; Fox, Z; Gerstoft, J; Justesen, US; Losso, M; Lundgren, JD; Obel, N; Pedersen, C; Peters, B, 2007
)
" Three infants (14%) had transient adverse events of grade 3 or more that were possibly related to study treatment but did not require permanent treatment discontinuation."( Pharmacokinetics, safety and efficacy of lopinavir/ritonavir in infants less than 6 months of age: 24 week results.
Capparelli, EV; Chadwick, EG; Chen, J; Hughes, M; Palumbo, P; Pinto, JA; Robbins, B; Rodman, JH; Serchuck, L; Smith, E; Yogev, R, 2008
)
" Data regarding demographics, clinical disease and antiretroviral treatment history, HIV-1 RNA copies/mL, CD4 T-cell counts [absolute (cells/microL) and percentages (%)], adverse events, clinical laboratory values, reasons for discontinuation of PIs, and concomitant medications were extracted from the database for PI-naive (first-line) and PI-experienced (second- or higher-line) PI use."( Long-term safety and effectiveness of ritonavir, nelfinavir, and lopinavir/ritonavir in antiretroviral-experienced HIV-infected children.
Burri, M; Nadal, D; Rode, R; Rudin, C; Shen, Y, 2008
)
"Long-term PI-based therapy seems to be safe and to result in durable virologic and immunologic effectiveness in HIV-1-infected antiretroviral-experienced children."( Long-term safety and effectiveness of ritonavir, nelfinavir, and lopinavir/ritonavir in antiretroviral-experienced HIV-infected children.
Burri, M; Nadal, D; Rode, R; Rudin, C; Shen, Y, 2008
)
"The study showed a high incidence of adverse events when a higher than standard dose of the new lopinavir/ritonavir tablets was combined with rifampicin."( High incidence of adverse events in healthy volunteers receiving rifampicin and adjusted doses of lopinavir/ritonavir tablets.
Aarnoutse, RE; Boeree, MJ; Burger, DM; Koopmans, PP; L'homme, RF; Nijland, HM; Rongen, GA; van Crevel, R; van Uden, P, 2008
)
" DRV/r had a lower incidence of possibly treatment-related grade 2-4 gastrointestinal-related adverse events (7 versus 14%) and treatment-related moderate-to-severe diarrhea (4 versus 10%) than LPV/r."( Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1-infected patients at week 48.
Andrade-Villanueva, J; De Meyer, S; De Pauw, M; Dejesus, E; Fourie, J; Khanlou, H; Lefebvre, E; Ortiz, R; Spinosa-Guzman, S; van Lunzen, J; Vangeneugden, T; Voronin, E, 2008
)
" Safety assessments included laboratory tests, vital signs, physical examination, 12-lead electrocardiogram recordings, and patients' reporting of adverse events."( Efficacy and safety of mirodenafil, a new oral phosphodiesterase type 5 inhibitor, for treatment of erectile dysfunction.
Ahn, TY; Choi, HK; Chung, WS; Jung, HG; Kim, JJ; Kim, SC; Kim, SW; Lee, SW; Min, KS; Moon, KH; Paick, JS; Park, JK; Park, K; Park, NC; Suh, JK; Yang, DY, 2008
)
" Most treatment-associated adverse events were of mild intensity, resolving spontaneously."( Efficacy and safety of mirodenafil, a new oral phosphodiesterase type 5 inhibitor, for treatment of erectile dysfunction.
Ahn, TY; Choi, HK; Chung, WS; Jung, HG; Kim, JJ; Kim, SC; Kim, SW; Lee, SW; Min, KS; Moon, KH; Paick, JS; Park, JK; Park, K; Park, NC; Suh, JK; Yang, DY, 2008
)
" Safety was analyzed by adverse events, laboratory values and vital signs."( Efficacy and safety of oral SK3530 for the treatment of erectile dysfunction in Korean men: a multicenter, randomized, double-blind, placebo-controlled, fixed dose, parallel group clinical trial.
Ahn, TY; Choi, HK; Jung, H; Kim, JJ; Kim, SC; Kim, SW; Lee, SW; Paick, JS; Park, JK; Park, K; Park, KS; Park, NC, 2008
)
" Treatment-related adverse events occurred in 32 patients."( Efficacy and safety of oral SK3530 for the treatment of erectile dysfunction in Korean men: a multicenter, randomized, double-blind, placebo-controlled, fixed dose, parallel group clinical trial.
Ahn, TY; Choi, HK; Jung, H; Kim, JJ; Kim, SC; Kim, SW; Lee, SW; Paick, JS; Park, JK; Park, K; Park, KS; Park, NC, 2008
)
" Serious adverse events were noted in 51 (12%) of 441 patients in the atazanavir/ritonavir group and in 42 (10%) of 437 patients in the lopinavir/ritonavir group."( Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study.
Andrade-Villanueva, J; Chetchotisakd, P; Corral, J; David, N; Echevarria, J; Mancini, M; McGrath, D; Molina, JM; Moyle, G; Percival, L; Thiry, A; Yang, R, 2008
)
" Twenty-five patients (62%) experienced at least one adverse event."( Three-year outcome data of second-line antiretroviral therapy in Ugandan adults: good virological response but high rate of toxicity.
Bates, M; Castelnuovo, B; Colebunders, R; John, L; Kamya, MR; Lutwama, F; Ronald, A; Spacek, LA,
)
" In the studies performed to date, darunavir has been well tolerated, with a better profile than that of the PIs used in control groups in terms of adverse effects such as diarrhea, gastrointestinal tolerability and lipid alterations."( [Safety and tolerability of darunavir].
Antela López, A, 2008
)
" Common clinical adverse events (AEs) were diarrhoea, nausea, fatigue and headache."( Antiviral activity and safety of aplaviroc, a CCR5 antagonist, in combination with lopinavir/ritonavir in HIV-infected, therapy-naïve patients: results of the EPIC study (CCR100136).
Adkison, KK; Berger, D; Bonny, T; Cimoch, P; Lamarca, A; Lazzarin, A; Madison, SJ; McCarty, D; Millard, J; Nichols, WG; Salvato, P; Smaill, FM; Teofilo, E; Yeni, P, 2009
)
" Adverse events were limited to transient grade 3 neutropenia in 3 subjects."( Early initiation of lopinavir/ritonavir in infants less than 6 weeks of age: pharmacokinetics and 24-week safety and efficacy.
Alvero, CG; Browning, R; Capparelli, E; Chadwick, EG; Hazra, R; Heckman, BE; Hughes, MD; Luzuriaga, K; Palumbo, P; Pinto, J; Purdue, L; Robbins, B; Rodman, J; Serchuck, L; Yogev, R, 2009
)
" Rates of discontinuation and adverse events, including diarrhea, were similar between arms."( A once-daily lopinavir/ritonavir-based regimen is noninferior to twice-daily dosing and results in similar safety and tolerability in antiretroviral-naive subjects through 48 weeks.
Bernstein, B; Cohen, DE; da Silva, BA; Fredrick, L; Gathe, J; Gibbs, S; Loutfy, MR; Marsh, T; Naylor, C; Podzamczer, D; Rubio, R, 2009
)
" Adverse event rate leading to study drug discontinuation was 5% in both arms."( Efficacy and safety of switching from boosted lopinavir to boosted atazanavir in patients with virological suppression receiving a LPV/r-containing HAART: the ATAZIP study.
Aranda, M; Arranz, JA; Blanco, JL; Clotet, B; Cosin, J; Cruceta, A; Dalmau, D; Domingo, P; Ferrer, E; García, I; Gatell, JM; Gutiérrez, F; Knobel, H; Lazzari, Ed; Llibre, JM; Mallolas, J; Martínez, E; Milinkovic, A; Murillas, J; Pedrol, E; Pich, J; Podzamczer, D; Ribera, E; Roca, V; Vidal, F, 2009
)
"Double-boosted SQV+LPV/r was an effective and safe alternative for a second-line regimen in children."( Safety and efficacy of a double-boosted protease inhibitor combination, saquinavir and lopinavir/ritonavir, in pretreated children at 96 weeks.
Ananworanich, J; Boonrak, P; Bunupuradah, T; Burger, D; Engchanil, C; Kosalaraksa, P; Lumbiganon, P; Mahanontharit, A; Mengthaisong, T; Puthanakit, T; Ruxrungtham, K; Tompkins, E; van der Lugt, J, 2009
)
"Primary endpoints were time to virologic failure (confirmed HIV-1 RNA > or = 1,000 copies/mL at 16-24 weeks or > or = 200 copies/mL at > or = 24 weeks) and time to first grade 3 or 4 adverse event or laboratory abnormality that was at least one grade higher than at baseline."( Virologic response and safety of the abacavir/lamivudine fixed-dose formulation as part of highly active antiretroviral therapy: analyses of six clinical studies.
Dix, LP; Ha, B; Liao, QM; Pappa, KA,
)
" Few subjects treated with ABC/3TC developed grade 3 or 4 adverse events, laboratory toxicities, or changes in lipid levels."( Virologic response and safety of the abacavir/lamivudine fixed-dose formulation as part of highly active antiretroviral therapy: analyses of six clinical studies.
Dix, LP; Ha, B; Liao, QM; Pappa, KA,
)
" Diarrhea was the most frequently reported adverse event."( Long-term efficacy and safety of fosamprenavir plus ritonavir versus lopinavir/ritonavir in combination with abacavir/lamivudine over 144 weeks.
Baril, JG; Duiculescu, D; Estrada, V; Lim, ML; Logue, K; Pharo, C; Plettenberg, A; Pulido, F; Schewe, K; Vavro, C; Yau, L,
)
" Treatment-related gastrointestinal adverse events were greater in patients taking lopinavir/ritonavir."( Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 96-week efficacy and safety results of the CASTLE study.
Absalon, J; Andrade-Villanueva, J; Chetchotisakd, P; Corral, J; David, N; Echevarria, J; Lataillade, M; Mancini, M; McGrath, D; Molina, JM; Moyle, G; Percival, L; Wirtz, V; Yang, R, 2010
)
" Atazanavir/ritonavir had a better lipid profile and fewer gastrointestinal adverse events than lopinavir/ritonavir."( Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 96-week efficacy and safety results of the CASTLE study.
Absalon, J; Andrade-Villanueva, J; Chetchotisakd, P; Corral, J; David, N; Echevarria, J; Lataillade, M; Mancini, M; McGrath, D; Molina, JM; Moyle, G; Percival, L; Wirtz, V; Yang, R, 2010
)
" The occurrence of treatment-related moderate/severe adverse events was comparable for all events except nausea, which was reported more frequently among BID-treated subjects."( Similar safety and efficacy of once- and twice-daily lopinavir/ritonavir tablets in treatment-experienced HIV-1-infected subjects at 48 weeks.
Andrade-Villanueva, J; Badal-Faesen, S; Bernstein, BM; Fredrick, LM; Gathe, J; Gaultier, IA; Mingrone, H; Podsadecki, TJ; Woodward, WC; Zajdenverg, R, 2010
)
"Long-term treatment with LPV/r-based cART is safe and effective in HIV-1-infected children."( Long-term safety and effectiveness of lopinavir/ritonavir in antiretroviral-experienced HIV-1-infected children.
Bucher, HC; Nadal, D; Rickenbach, M; Rudin, C; Wolbers, M, 2010
)
" The safety assessments included laboratory tests, vital signs, 12-lead electrocardiogram recordings, and patients' reporting of adverse events."( Efficacy and safety of mirodenafil in men taking antihypertensive medications.
Kim, JJ; Kim, SC; Min, KS; Moon, KH; Paick, JS; Park, K; Suh, JK; Yang, DY, 2010
)
" Facial flushing and headache were the most common treatment-associated adverse events, which were mild or moderate in severity, resolving spontaneously."( Efficacy and safety of mirodenafil in men taking antihypertensive medications.
Kim, JJ; Kim, SC; Min, KS; Moon, KH; Paick, JS; Park, K; Suh, JK; Yang, DY, 2010
)
"Mirodenafil was effective and safe in men with ED concomitantly taking antihypertensive medications."( Efficacy and safety of mirodenafil in men taking antihypertensive medications.
Kim, JJ; Kim, SC; Min, KS; Moon, KH; Paick, JS; Park, K; Suh, JK; Yang, DY, 2010
)
"Successful treatment of chronic hepatitis B (CHB) often requires long-term oral nucleoside/nucleotide agents which can be associated with viral resistance, patient non-compliance and adverse effects."( Safety evaluation of telbivudine.
But, DY; Fung, J; Lai, CL; Yuen, MF, 2010
)
" Viral resistance, characteristic adverse effects including elevation in creatine kinase and peripheral neuropathy in telbivudine treatment are reviewed."( Safety evaluation of telbivudine.
But, DY; Fung, J; Lai, CL; Yuen, MF, 2010
)
" Creatine kinase elevation is not a good predictor of muscle-related adverse effects with nucleoside/nucleotide analogs."( Safety evaluation of telbivudine.
But, DY; Fung, J; Lai, CL; Yuen, MF, 2010
)
" Through 96 weeks, 77 subjects from each group discontinued prematurely; adverse or HIV-related events contributed to discontinuation of 36 subjects overall, with no significant differences between treatment groups."( Short communication: Comparable safety and efficacy with once-daily versus twice-daily dosing of lopinavir/ritonavir tablets with emtricitabine + tenofovir DF in antiretroviral-naïve, HIV type 1-infected subjects: 96 week final results of the randomized t
Bernstein, B; Cohen, D; da Silva, B; Fredrick, L; González-García, J; Johnson, M; Naylor, C; Sloan, L, 2010
)
" In part B, neutropenia remained the most commonly reported causally related adverse event."( A Phase I study to assess the safety, tolerability, and pharmacokinetics of AZD4877, an intravenous Eg5 inhibitor in patients with advanced solid tumors.
Burris, HA; Eckhardt, SG; Herbst, RS; Huszar, D; Hylander-Gans, L; Infante, JR; Kurzrock, R; Li, J; Osmukhina, A; Skolnik, JM; Spratlin, J; Wu, K, 2012
)
" No serious adverse events were noted in the telbivudine-treated mothers or their infants."( A prospective and open-label study for the efficacy and safety of telbivudine in pregnancy for the prevention of perinatal transmission of hepatitis B virus infection.
Bai, SF; Cao, MK; Fang, ZX; Han, GR; Jiang, HX; Tang, X; Wang, CM; Wang, GJ; Yue, X; Zhao, W, 2011
)
"This study was conducted to determine whether mirodenafil 100 mg, when administered on demand to patients with benign prostatic hyperplasia (BPH) who are receiving α1-blocker therapy, is safe with regard to the cardiovascular system and whether it improves lower urinary tract symptoms (LUTS) and sexual function."( Efficacy and safety of combination therapy with mirodenafil and α1-blocker for benign prostatic hyperplasia-induced lower urinary tract symptoms accompanied by erectile dysfunction: a multicenter, open-label, prospective study.
Cho, SY; Ha, US; Lee, JY; Lee, SH; Lee, SW; Moon, HS; Oh, CY; Park, SY,
)
" No telbivudine discontinuations occurred from adverse events, and no congenital deformities were observed in the infants delivered to telbivudine-treated mothers."( [Efficacy and safety of telbivudine in pregnant women to prevent perinatal transmission of hepatitis B virus].
Han, GR; Jiang, HX; Kan, NY; Wang, CM; Wang, GJ; Wu, MM; Yue, X, 2012
)
" Adverse events were defined with common toxicity criteria, and tumour response was measured by Response Evaluation Criteria In Solid Tumors."( Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial.
Becerra, C; Bendell, JC; Burris, HA; Cox, DS; DeMarini, DJ; Eckhardt, G; Falchook, GS; Fecher, LA; Flaherty, K; Gordon, MS; Hart, L; Infante, JR; Kurzrock, R; Le, NT; Messersmith, WA; Morris, SR; Nallapareddy, S; Peddareddigari, VG; Xu, Y, 2012
)
" Dose-limiting toxic effects included rash (n=2), diarrhoea (n=1), and central serous retinopathy (n=2)."( Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial.
Becerra, C; Bendell, JC; Burris, HA; Cox, DS; DeMarini, DJ; Eckhardt, G; Falchook, GS; Fecher, LA; Flaherty, K; Gordon, MS; Hart, L; Infante, JR; Kurzrock, R; Le, NT; Messersmith, WA; Morris, SR; Nallapareddy, S; Peddareddigari, VG; Xu, Y, 2012
)
" With the increased realization of receptive anal intercourse among heterosexual couples often in conjunction with vaginal intercourse, having a safe and effective microbicide for both mucosal sites is critical."( Safety and efficacy of tenofovir/IQP-0528 combination gels - a dual compartment microbicide for HIV-1 prevention.
Buckheit, KW; Buckheit, RW; Dezzutti, CS; Gwozdz, G; Mahalingam, A; Shetler, C; Ugaonkar, SR, 2012
)
" Facial flushing was the most common adverse effect, followed by headaches."( Safety and efficacy of once daily administration of 50 mg mirodenafil in patients with erectile dysfunction: a multicenter, double-blind, placebo controlled trial.
Cho, JM; Chung, JH; Chung, JM; Kang, DH; Kim, TH; Lee, KS; Lee, SW; Lee, W; Moon, KH; Oh, CY, 2013
)
"Once daily administration of 50 mg mirodenafil was efficacious and safe for the treatment of erectile dysfunction and lower urinary tract symptoms."( Safety and efficacy of once daily administration of 50 mg mirodenafil in patients with erectile dysfunction: a multicenter, double-blind, placebo controlled trial.
Cho, JM; Chung, JH; Chung, JM; Kang, DH; Kim, TH; Lee, KS; Lee, SW; Lee, W; Moon, KH; Oh, CY, 2013
)
" Safety was assessed by evaluating cardiovascular parameters and the participant-reported treatment-emergent adverse events (TEAEs)."( Efficacy and safety of the simultaneous administration of mirodenafil and an α-blocker in men with BPH-LUTS: a multicenter open-label prospective study.
Bang, WJ; Cho, JS; Chung, BH; Lee, DH; Lee, SH; Oh, CY; Yang, DY; Yoo, C,
)
" The most commonly reported treatment-related adverse events (TRAEs) were neutropenia (22 patients), fatigue (12), leukopenia (7) and constipation (6); the most commonly reported grade ≥ 3 TRAE was neutropenia (21)."( Phase II study to assess the efficacy, safety and tolerability of the mitotic spindle kinesin inhibitor AZD4877 in patients with recurrent advanced urothelial cancer.
Albers, P; Arranz, JA; Chester, J; Chowdhury, S; Dudek, AZ; Elliott, T; Grimm, MO; Gschwend, JE; Hudes, G; Jones, R; Li, J; Mead, G; Müller-Mattheis, V; Osmukhina, A; Skolnik, J; Vuky, J; Wülfing, C, 2013
)
" Outcome measures assessed were the International Index of Erectile Function (IIEF), erectile function domain (EFD) score (primary), the Sexual Encounter Profile questions 2 and 3, and the response to the Global Assessment Questionnaire and adverse effects (secondary)."( Efficacy and safety of mirodenafil for patients with erectile dysfunction: a meta-analysis of three multicenter, randomized, double-blind, placebo-controlled clinical trials.
Ding, H; Du, W; Fan, N; Li, J; Shang, P; Wang, Z, 2014
)
" The most common drug-related adverse events were flushing and headache (mirodenafil versus placebo: 15."( Efficacy and safety of mirodenafil for patients with erectile dysfunction: a meta-analysis of three multicenter, randomized, double-blind, placebo-controlled clinical trials.
Ding, H; Du, W; Fan, N; Li, J; Shang, P; Wang, Z, 2014
)
" Overall, RPL554 was well tolerated, and adverse events were generally mild and of equal frequency between placebo and active treatment groups."( Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials.
Banner, KH; Burggraaf, J; Calzetta, L; Cazzola, M; Cohen, AF; de Kam, ML; Diamant, Z; Franciosi, LG; Kamerling, IM; Morelli, N; Page, CP; Singh, D; Spina, D; Walker, MJ; Zuiker, R, 2013
)
" In the Phase III study testing dabrafenib, 53% of patients reported grade 2 or higher adverse events (AEs)."( Dabrafenib for the treatment of BRAF V600-positive melanoma: a safety evaluation.
Blank, C; Rutkowski, P, 2014
)
" Patients' adverse events were recorded in a specific database."( Cutaneous adverse events in patients treated with BRAF inhibitor-based therapies for metastatic melanoma for longer than 52 weeks.
Anforth, R; Carlos, G; Clements, A; Fernandez-Peñas, P; Kefford, R, 2015
)
"Patients continued to develop cutaneous adverse events after 52 weeks of continuous therapy."( Cutaneous adverse events in patients treated with BRAF inhibitor-based therapies for metastatic melanoma for longer than 52 weeks.
Anforth, R; Carlos, G; Clements, A; Fernandez-Peñas, P; Kefford, R, 2015
)
"BRAF inhibitor (BRAFi) and MEK inhibitor (MEKi) frequently cause cutaneous adverse events."( Comparative profile of cutaneous adverse events: BRAF/MEK inhibitor combination therapy versus BRAF monotherapy in melanoma.
Algazi, A; Chong, K; Choudhry, A; Daud, A; Johnston, K; Meier, M; Ortiz-Urda, S; Osella-Abate, S; Posch, C; Quaglino, P; Rappersberger, K; Sanlorenzo, M; Vujic, I, 2014
)
" Patient characteristics, and the occurrence and severity of cutaneous adverse events, are described."( Comparative profile of cutaneous adverse events: BRAF/MEK inhibitor combination therapy versus BRAF monotherapy in melanoma.
Algazi, A; Chong, K; Choudhry, A; Daud, A; Johnston, K; Meier, M; Ortiz-Urda, S; Osella-Abate, S; Posch, C; Quaglino, P; Rappersberger, K; Sanlorenzo, M; Vujic, I, 2014
)
"The development of cutaneous adverse events was significantly less frequent (P = ."( Comparative profile of cutaneous adverse events: BRAF/MEK inhibitor combination therapy versus BRAF monotherapy in melanoma.
Algazi, A; Chong, K; Choudhry, A; Daud, A; Johnston, K; Meier, M; Ortiz-Urda, S; Osella-Abate, S; Posch, C; Quaglino, P; Rappersberger, K; Sanlorenzo, M; Vujic, I, 2014
)
"Combination regimen with BRAFi and MEKi shows fewer cutaneous adverse events and longer cutaneous adverse event-free interval compared with BRAFi monotherapy."( Comparative profile of cutaneous adverse events: BRAF/MEK inhibitor combination therapy versus BRAF monotherapy in melanoma.
Algazi, A; Chong, K; Choudhry, A; Daud, A; Johnston, K; Meier, M; Ortiz-Urda, S; Osella-Abate, S; Posch, C; Quaglino, P; Rappersberger, K; Sanlorenzo, M; Vujic, I, 2014
)
"The cutaneous adverse effects of the BRAF inhibitors vemurafenib and dabrafenib mesylate in the treatment of metastatic melanoma have been well reported."( Cutaneous Toxic Effects of BRAF Inhibitors Alone and in Combination With MEK Inhibitors for Metastatic Melanoma.
Anforth, R; Carlino, MS; Carlos, G; Chou, S; Clements, A; Fernandez-Peñas, P; Menzies, AM, 2015
)
"To compare the cutaneous toxic effects of BRAF inhibitor monotherapy and CombiDT therapy in a large cohort of patients."( Cutaneous Toxic Effects of BRAF Inhibitors Alone and in Combination With MEK Inhibitors for Metastatic Melanoma.
Anforth, R; Carlino, MS; Carlos, G; Chou, S; Clements, A; Fernandez-Peñas, P; Menzies, AM, 2015
)
"Multiple cutaneous adverse effects between BRAF inhibitor monotherapy and CombiDT therapy were identified and compared in a cohort of patients who underwent the same dermatologic assessment."( Cutaneous Toxic Effects of BRAF Inhibitors Alone and in Combination With MEK Inhibitors for Metastatic Melanoma.
Anforth, R; Carlino, MS; Carlos, G; Chou, S; Clements, A; Fernandez-Peñas, P; Menzies, AM, 2015
)
"The most common cutaneous adverse effects seen in patients receiving the single-agent BRAF inhibitor dabrafenib or vemurafenib included Grover disease (51 patients [42."( Cutaneous Toxic Effects of BRAF Inhibitors Alone and in Combination With MEK Inhibitors for Metastatic Melanoma.
Anforth, R; Carlino, MS; Carlos, G; Chou, S; Clements, A; Fernandez-Peñas, P; Menzies, AM, 2015
)
"This study confirms that the prevalence of cutaneous toxic effects differs among vemurafenib, dabrafenib, and CombiDT therapies."( Cutaneous Toxic Effects of BRAF Inhibitors Alone and in Combination With MEK Inhibitors for Metastatic Melanoma.
Anforth, R; Carlino, MS; Carlos, G; Chou, S; Clements, A; Fernandez-Peñas, P; Menzies, AM, 2015
)
" Although this approach has improved survival rates, the high doses of chemotherapy required for clinical efficacy often result in lasting neurocognitive defects and other adverse events."( A WEE1 Inhibitor Analog of AZD1775 Maintains Synergy with Cisplatin and Demonstrates Reduced Single-Agent Cytotoxicity in Medulloblastoma Cells.
Amani, V; Backos, DS; Donson, AM; Foreman, NK; Harris, PS; Matheson, CJ; Reigan, P; Venkataraman, S; Vibhakar, R; Wempe, MF, 2016
)
" Cutaneous adverse events have been reported, but hair and nail data have been rarely detailed."( Hair and nail adverse events during treatment with targeted therapies for metastatic melanoma.
Dika, E; Fanti, PA; Melotti, B; Patrizi, A; Piraccini, BM; Ribero, S; Sperandi, F; Starace, M, 2016
)
" Although they have shown promising results, they also have caused multiple adverse events (AEs), particularly immune-related AEs (irAEs)."( Novel melanoma therapies and their side effects.
González, N; Ratner, D, 2016
)
"All patients presented with at least 1 adverse skin reaction."( Prospective Case Series of Cutaneous Adverse Effects Associated With Dabrafenib and Trametinib.
Lacroix, JP; Wang, B,
)
"Selective BRAF inhibitor dabrafenib and MEK inhibitor trametinib are associated with multiple skin adverse effects."( Prospective Case Series of Cutaneous Adverse Effects Associated With Dabrafenib and Trametinib.
Lacroix, JP; Wang, B,
)
" Our algorithm, based on partial least squares-discriminant analysis (PLS-DA) and cross-validation by bootstrapping, discriminated to variable degrees spectra from patient suffering and not suffering cutaneous adverse events."( A Novel Spectroscopically Determined Pharmacodynamic Biomarker for Skin Toxicity in Cancer Patients Treated with Targeted Agents.
Azan, A; Bakker Schut, TC; Besse, B; Boutros, C; Caspers, PJ; Eggermont, AM; Kamsu Kom, N; Koljenović, S; Lanoy, E; Mateus, C; Mir, LM; Noordhoek Hegt, V; Paci, A; Planchard, D; Puppels, GJ; Robert, C; Routier, E; Roy, S; Seck, A; Texier, M; Tomasic, G, 2017
)
" The combination of BRAF inhibitor dabrafenib with MEK inhibitor trametinib has shown its superiority to single agent therapy and is characterized by a tolerable spectrum of adverse events which shows a decrease in incidence over time on treatment."( The safety and efficacy of dabrafenib and trametinib for the treatment of melanoma.
Kanaki, T; Knispel, S; Livingstone, E; Schadendorf, D; Ugurel, S; Zimmer, L, 2018
)
" Phase 1 was primarily intended to assess safety and tolerability as assessed by adverse events (AE), and the primary end-point in phase 2 was to assess confirmed overall response rate (ORR)."( Phase 1/2 study assessing the safety and efficacy of dabrafenib and trametinib combination therapy in Japanese patients with BRAF V600 mutation-positive advanced cutaneous melanoma.
Fujiwara, Y; Kiyohara, Y; Kondo, S; Mukaiyama, A; Namikawa, K; Takahashi, A; Tsutsumida, A; Yamazaki, N; Yoshikawa, S; Zhang, F, 2018
)
" The incidence of drug-related adverse events was 18."( Long-term safety and efficacy of the novel β
Kakizaki, H; Kurose, T; Nagai, S; Takahashi, S; Yoshida, M, 2018
)
" Data suggest that immune-related adverse events (irAEs) are associated with clinical benefit in patients treated with immunotherapy and that response to BRAF/MEK therapy may have an underlying immune mechanism."( Possible immune adverse events as predictors of durable response to BRAF inhibitors in patients with BRAF V600-mutant metastatic melanoma.
Asher, N; Baruch, EN; Ben-Betzalel, G; Boursi, B; Markel, G; Schachter, J; Shapira-Frommer, R; Steinberg-Silman, Y, 2018
)
" Treatment-emergent adverse events (TEAEs) occurred in 31 patients (66%) taking BAY 85-8501 and in 36 patients (77%) taking placebo, and were mostly mild or moderate."( Safety and efficacy of the human neutrophil elastase inhibitor BAY 85-8501 for the treatment of non-cystic fibrosis bronchiectasis: A randomized controlled trial.
Bandel, TJ; Kirsten, A; Nagelschmitz, J; Pedersen, F; Rabe, KF; Schwers, S; van der Mey, D; Watz, H, 2019
)
" In clinical trials, the most common digestive adverse events were nausea, vomiting, and diarrhoea."( Severe gastrointestinal toxicity of MEK inhibitors.
Allayous, C; Allez, M; Ballon, A; Baroudjian, B; Bertheau, P; Delyon, J; Eftekhari, P; Lebbé, C; Lourenço, N; Mourad, N; Pagès, C, 2019
)
" In addition, dabrafenib-trametinib has a favorable effect on Grades 3 and 4 adverse events."( Efficacy and safety of dabrafenib-trametinib in the treatment of unresectable advanced/metastatic melanoma with BRAF-V600 mutation: A systematic review and network meta-analysis.
Castañeda-Cardona, C; Castrillón, J; Garzón-Orjuela, N; González-Bravo, D; Herrera, D; Lasalvia, P; Prieto-Pinto, L; Rosselli, D, 2020
)
" We retrieved evidence on treatment-related grade III/IV adverse events, progression-free survival (PFS) and overall survival (OS)."( A systematic literature review and network meta-analysis of effectiveness and safety outcomes in advanced melanoma.
Franken, MG; Gheorghe, M; Haanen, JBAG; Leeneman, B; Uyl-de Groot, CA; van Baal, PHM, 2019
)
" Adverse events occurred in 88% of cases; 16% were grade 3 or worse."( Real-world efficacy and safety data for dabrafenib and trametinib combination therapy in Japanese patients with BRAF V600 mutation-positive advanced melanoma.
Nakano, E; Namikawa, K; Takahashi, A; Yamazaki, N, 2020
)
" Grade ≥ 3 adverse events reported most commonly in any cohort included: anemia; decreased white blood cell count; decreased neutrophil count; neutropenia; decreased platelet count; thrombocytopenia; and febrile neutropenia."( Safety, Pharmacokinetics, and Clinical Activity of Adavosertib in Combination with Chemotherapy in Asian Patients with Advanced Solid Tumors: Phase Ib Study.
Bang, YJ; de Souza, P; Kato, H; Kim, SW; Kumar, S; Lickliter, JD; Mugundu, GM; Naito, Y; Park, K, 2020
)
" Dry mouth, drug-related treatment-emergent adverse event (TEAE), serious adverse event (SAE), and discontinuations due to adverse event (AE) suggested that Vibegron was well tolerated."( The efficacy and safety of Vibegron in treating overactive bladder: A systematic review and pooled analysis of randomized controlled trials.
Chen, H; Cui, Y; Shi, H; Zhang, Y, 2020
)
"Various adverse events (AEs) have been reported to occur at a high rate in patients treated with dabrafenib plus trametinib (D + T) combination therapy."( Serum soluble CD163 and proinflammatory chemokines may be biomarkers of the onset of adverse events in dabrafenib plus trametinib combination therapy for advanced melanoma.
Aiba, S; Amagai, R; Fujimura, T; Furudate, S; Hashimoto, A; Kambayashi, Y; Muto, Y; Ohuchi, K; Okuma, T, 2021
)
" However, additional studies have revealed potential adverse effects with KPR-2579, such as the formation of a reactive metabolite, CYP3A4 induction, and convulsions."( Identification of N-acyl-N-indanyl-α-phenylglycinamides as selective TRPM8 antagonists designed to mitigate the risk of adverse effects.
Fujimori, Y; Hirasawa, H; Ikeda, T; Kamada, N; Kanbe, H; Kobayashi, JI; Nakanishi, O; Yamamoto, A, 2021
)
" The primary outcome was safety, measured by incidence of adverse events."( Once-Daily Vibegron 75 mg for Overactive Bladder: Long-Term Safety and Efficacy from a Double-Blind Extension Study of the International Phase 3 Trial (EMPOWUR).
Frankel, J; Jankowich, R; Mudd, PN; Shortino, D; Staskin, D; Varano, S, 2021
)
"4%) discontinued owing to adverse events."( Once-Daily Vibegron 75 mg for Overactive Bladder: Long-Term Safety and Efficacy from a Double-Blind Extension Study of the International Phase 3 Trial (EMPOWUR).
Frankel, J; Jankowich, R; Mudd, PN; Shortino, D; Staskin, D; Varano, S, 2021
)
" Outcomes of interest included recurrence-free survival (RFS)/disease-free survival (DFS), distant metastasis-free survival (DMFS), all-cause grade 3/4 adverse events (AEs), discontinuations, and discontinuations due to AEs."( Comparative efficacy and safety of adjuvant nivolumab versus other treatments in adults with resected melanoma: a systematic literature review and network meta-analysis.
Amadi, A; Chan, K; Kotapati, S; Middleton, MR; Moshyk, A; Toor, K, 2021
)
" Safety was assessed through adverse events (AEs)."( Efficacy and Safety of Once-Daily Vibegron for Treatment of Overactive Bladder in Patients Aged ≥65 and ≥75 Years: Subpopulation Analysis from the EMPOWUR Randomized, International, Phase III Study.
Frankel, J; Jankowich, R; Mudd, PN; Shortino, D; Staskin, D; Varano, S, 2021
)
"In this subpopulation analysis of patients with OAB aged ≥ 65 and ≥ 75 years from the EMPOWUR study, once-daily vibegron 75 mg showed rapid onset and robust efficacy versus placebo and was generally safe and well tolerated, consistent with results from the overall population."( Efficacy and Safety of Once-Daily Vibegron for Treatment of Overactive Bladder in Patients Aged ≥65 and ≥75 Years: Subpopulation Analysis from the EMPOWUR Randomized, International, Phase III Study.
Frankel, J; Jankowich, R; Mudd, PN; Shortino, D; Staskin, D; Varano, S, 2021
)
" Maximum flow rate and residual urine volume did not change, and no patient discontinued vibegron because of adverse events."( Efficacy and Safety of Vibegron Add-on Therapy in Men With Persistent Storage Symptoms After Receiving Alpha 1-Blocker or Phosphodiesterase 5 Inhibitor: A Preliminary Study.
Hiramatsu, I; Honda, S; Horie, S; Ishikawa, K; Iwata, S; Mitsuhashi, I; Miyoshi, M; Miyoshi, Y; Mizuno, T; Noto, K; Nozaki, T; Ogasa, T; Shigeta, Y; Shirai, M; Sugimura, S; Tsujimura, A; Uesaka, Y, 2021
)
" With regard to dry mouth and drug related treatment-emergent adverse event (TEAE), vibegron showed better tolerance than antimuscarinic."( Systematic review and meta-analysis of the efficacy and safety of vibegron vs antimuscarinic monotherapy for overactive bladder.
Chen, Z; Gao, Y; Liang, L; Lin, J; Liu, L; Su, S, 2021
)
" Treatment-related adverse events occurred in all patients (100%); most (89%) were grade 1-2."( Efficacy and Safety of Trametinib in Non-V600 BRAF Mutant Melanoma: A Phase II Study.
Amaria, RN; Davies, MA; Flaherty, KT; Johnson, DB; Nebhan, CA; Sosman, JA; Sullivan, RJ, 2021
)
"Cardiovascular adverse events (CVAEs) associated with BRAF inhibitors alone versus combination BRAF/MEK inhibitors are not fully understood."( Cardiovascular adverse events associated with BRAF versus BRAF/MEK inhibitor: Cross-sectional and longitudinal analysis using two large national registries.
Al-Kindi, S; Barnholtz-Sloan, JS; de Lima, M; Dowlati, A; Fradley, MG; Guha, A; Gutierrez, JM; Jain, C; Jain, P; Lenihan, D; Oliveira, GH, 2021
)
" We utilized the cross-sectional FDA's Adverse Events Reporting System (FAERS) and longitudinal Truven Health Analytics/IBM MarketScan database from 2011 to 2018."( Cardiovascular adverse events associated with BRAF versus BRAF/MEK inhibitor: Cross-sectional and longitudinal analysis using two large national registries.
Al-Kindi, S; Barnholtz-Sloan, JS; de Lima, M; Dowlati, A; Fradley, MG; Guha, A; Gutierrez, JM; Jain, C; Jain, P; Lenihan, D; Oliveira, GH, 2021
)
"4%) were cardiovascular adverse events (mortality rate 19%)."( Cardiovascular adverse events associated with BRAF versus BRAF/MEK inhibitor: Cross-sectional and longitudinal analysis using two large national registries.
Al-Kindi, S; Barnholtz-Sloan, JS; de Lima, M; Dowlati, A; Fradley, MG; Guha, A; Gutierrez, JM; Jain, C; Jain, P; Lenihan, D; Oliveira, GH, 2021
)
" Adverse events were slightly increased in the ≥65-year subgroup."( Cardiovascular safety of vibegron, a new β3-adrenoceptor agonist, in older patients with overactive bladder: Post-hoc analysis of a randomized, placebo-controlled, double-blind comparative phase 3 study.
Gotoh, M; Kakizaki, H; Masumori, N; Minemura, K; Nagai, S; Takahashi, S; Takeda, M; Yokoyama, O; Yoshida, M, 2021
)
" The primary outcome was safety, including bone mineral density (BMD) and treatment-emergent adverse events (TEAEs)."( Relugolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, in women with endometriosis-associated pain: phase 2 safety and efficacy 24-week results.
Kudou, K; Kusumoto, T; Osuga, Y; Seki, Y; Tanimoto, M; Terakawa, N, 2021
)
" Target drug-associated AKI signals were detected by reporting odds ratio (ROR) derived from report data in the Food and Drug Administration Adverse Events Reporting System database."( BRAF/MEK inhibitor-associated nephrotoxicity in a real-world setting and human kidney cells.
Hotta, Y; Kataoka, T; Kimura, K; Mori, N; Sanagawa, A; Tohkin, M; Tomita, N, 2021
)
" Safety was assessed by clinical examinations and adverse events."( A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TPN171H, a Novel Phosphodiesterase Type 5 Inhibitor, in Healthy Subjects.
Chen, Q; Jia, J; Jiang, H; Li, T; Liang, L; Pu, H; Qian, H; Shen, J; Song, R; Tian, G; Wang, Y; Wang, Z; Xin, L; Yu, C; Zhu, H; Zou, Y, 2021
)
"TPN171H was safe and generally tolerated in healthy subjects."( A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TPN171H, a Novel Phosphodiesterase Type 5 Inhibitor, in Healthy Subjects.
Chen, Q; Jia, J; Jiang, H; Li, T; Liang, L; Pu, H; Qian, H; Shen, J; Song, R; Tian, G; Wang, Y; Wang, Z; Xin, L; Yu, C; Zhu, H; Zou, Y, 2021
)
" COMBI-APlus evaluated whether an adapted pyrexia management algorithm reduces high-grade pyrexia and pyrexia-related adverse outcomes."( Improved pyrexia-related outcomes associated with an adapted pyrexia adverse event management algorithm in patients treated with adjuvant dabrafenib plus trametinib: Primary results of COMBI-APlus.
Atkinson, V; Banerjee, H; Del Vecchio, M; Demidov, L; Dutriaux, C; Gogas, H; Grob, JJ; Gupta, A; Lau, M; Menzies, AM; Miranda, F; Robert, C; Ryll, B, 2022
)
" The most common adverse events were consistent with those in COMBI-AD, and 14."( Improved pyrexia-related outcomes associated with an adapted pyrexia adverse event management algorithm in patients treated with adjuvant dabrafenib plus trametinib: Primary results of COMBI-APlus.
Atkinson, V; Banerjee, H; Del Vecchio, M; Demidov, L; Dutriaux, C; Gogas, H; Grob, JJ; Gupta, A; Lau, M; Menzies, AM; Miranda, F; Robert, C; Ryll, B, 2022
)
" Serious adverse events occurred in three patients, one of which was possibly related to PRI-724."( Safety, tolerability, and anti-fibrotic efficacy of the CBP/β-catenin inhibitor PRI-724 in patients with hepatitis C and B virus-induced liver cirrhosis: An investigator-initiated, open-label, non-randomised, multicentre, phase 1/2a study.
Harada, K; Ieiri, I; Ikura, Y; Imamura, J; Inoue, K; Ishikawa, T; Kamisawa, T; Kanto, T; Kimura, K; Kimura, M; Kishimoto, J; Nishikawa, K; Ogawa, E; Okusaka, T; Saio, M; Shimoda, S; Todaka, K, 2022
)
" There were no differences in adverse events (AEs) rate or grade between the groups."( Safety of combining dabrafenib plus trametinib in elderly BRAF V600 mutation-positive advanced melanoma patients: real-world data analysis of Spanish patients (ELDERLYMEL).
Aguado, C; Cabrera Suárez, MÁ; Castellón Rubio, VE; España, S; García-Castaño, A; González-Barrallo, I; Majem, M; Martínez-Fernández, A; Medina, J; Mujika, K; Osterloh, L; Palacio, I, 2022
)
" Safety was assessed through adverse events (AEs)."( Efficacy and Safety of Vibegron for the Treatment of Overactive Bladder in Women: A Subgroup Analysis From the Double-Blind, Randomized, Controlled EMPOWUR Trial.
Greene, H; Haag-Molkenteller, C; Newman, DK; Thomas, E; Varano, S, 2023
)
"In this subgroup analysis, women receiving vibegron showed significant reductions in key efficacy end points versus placebo and favorable safety profile, consistent with the overall results from EMPOWUR, suggesting that vibegron is efficacious and safe for the treatment of OAB in this patient population."( Efficacy and Safety of Vibegron for the Treatment of Overactive Bladder in Women: A Subgroup Analysis From the Double-Blind, Randomized, Controlled EMPOWUR Trial.
Greene, H; Haag-Molkenteller, C; Newman, DK; Thomas, E; Varano, S, 2023
)
" The most common treatment-related adverse events (AEs) were diarrhea (56."( A Phase Ib Study Assessing the Safety, Tolerability, and Efficacy of the First-in-Class Wee1 Inhibitor Adavosertib (AZD1775) as Monotherapy in Patients with Advanced Solid Tumors.
Bauer, TM; Beck, JT; Chmielecki, J; Chu, Q; Fu, S; Hart, L; Imedio, ER; Jenkins, S; Jones, S; Kumar, S; Mita, AC; Moore, KN; Mugundu, G; Oza, A; Rader, JS; Simpkins, F; Spigel, D; Tinker, AV, 2023
)

Pharmacokinetics

ExcerptReference
"1 mg/kg) were below the assay's limit of detection and were not included in the pharmacokinetic analysis."( Pharmacokinetic and tolerance evaluation of actisomide, a new antiarrhythmic agent, in healthy volunteers.
Dean, RR; Destache, CJ; Hilleman, DE; Malesker, MA; Mohiuddin, SM; Sketch, MH; Stoysich, A, 1991
)
" The terminal half-life of actisomide was similar (1."( Pharmacokinetics of a novel antiarrhythmic drug, actisomide.
Anderson, S; Cook, CS; Karim, A; Rozek, LF; Schoenhard, GL; Stolzenbach, J, 1993
)
" The results of pharmacokinetic studies suggest that the compound LM-1554 is poorly absorbed from the gastrointestinal tract after the oral administration in dogs and rabbits."( Mechanism of the antihyperlipaemic activity and pharmacokinetics of 2-chloromethyl-5,6,7,8-tetrahydrobenzo(b)thieno[2,3-d]pyrimidin-4(3H)-o ne.
Gandhi, TR; Goyal, RK; Jain, KS; Rathod, IS; Shishoo, CJ, 1997
)
" After iv administration of YH1885, 5-20 mg kg(-1), to rats, the pharmacokinetic parameters of YH1885 seem to be independent of the drug at the dose ranges studied."( Pharmacokinetics of a new reversible proton pump inhibitor, YH1885, after intravenous and oral administrations to rats and dogs: hepatic first-pass effect in rats.
Han, KS; Kim, YG; Lee, JW; Lee, MG; Yoo, JK, 1998
)
" With the exception of male rat, Tmax occurred at approximately 1 h or less."( Pharmacokinetics and metabolism of sildenafil in mouse, rat, rabbit, dog and man.
Ackland, MJ; James, GC; Muirhead, GJ; Rance, DJ; Walker, DK; Wastall, P; Wright, PA, 1999
)
"To investigate the effect of the antiretroviral protease inhibitors saquinavir (soft gelatin capsule) and ritonavir on the pharmacokinetic properties and tolerability of sildenafil and to investigate the effect of sildenafil on the steady-state pharmacokinetics of saquinavir and ritonavir."( Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir.
Buss, N; Fielding, A; Kleinermans, D; Muirhead, GJ; Wulff, MB, 2000
)
"Both protease inhibitors significantly increased Cmax, AUC, tmax and t(1/2) values for both sildenafil and UK-103, 320."( Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir.
Buss, N; Fielding, A; Kleinermans, D; Muirhead, GJ; Wulff, MB, 2000
)
" Pharmacokinetic studies in rats and dogs indicated that 2u was absorbed rapidly after oral administration and had satisfactory bioavailability in these experimental animal species (rat, 17%; dog, 32%)."( Synthesis, structure-activity relationships, and pharmacokinetic profiles of nonpeptidic difluoromethylene ketones as novel inhibitors of human chymase.
Akahoshi, F; Ashimori, A; Eda, M; Fukaya, C; Imada, T; Kuwahara, S; Mitsutomi, N; Miyazaki, M; Nakajima, M; Nakamura, N; Ohtsuka, T; Sakashita, H; Yoshimura, T, 2001
)
" Lower clearance in dog (14 ml min(-1) kg(-1)) was the primary factor resulting in a longer elimination half-life (3."( Pharmacokinetics and metabolism of a selective PDE5 inhibitor (UK-343,664) in rat and dog.
Beaumont, KC; Comby, P; Evans, KM; Gedge, JI; Halliday, RC; Roffey, SJ; Walker, DK; Wright, PA,
)
" Over this 27-fold dose range, Cmax and AUCt increased 247- and 287-fold respectively."( Potential role for P-glycoprotein in the non-proportional pharmacokinetics of UK-343,664 in man.
Abel, S; Beaumont, KC; Crespi, CL; Eve, MD; Fox, L; Hyland, R; Jones, BC; Muirhead, GJ; Smith, DA; Venn, RF; Walker, DK,
)
" Based on its pharmacokinetic profile and a relative uroselectivity 29-fold greater than the nonselective drugs, fiduxosin is expected to exhibit greater selectivity for urethral compared with vascular alpha(1)-adrenoceptors in human and should be a novel, long-acting, uroselective alpha(1)-adrenoceptor antagonist."( Modeling of relationships between pharmacokinetics and blockade of agonist-induced elevation of intraurethral pressure and mean arterial pressure in conscious dogs treated with alpha(1)-adrenoceptor antagonists.
Brune, ME; Hancock, AA; Hui, YH; Katwala, SP; Kerwin, JF; Marsh, KC; Meyer, MD; Milicic, I; Stolarik, D; Witte, DG, 2002
)
"Significant differences in Cmax and AUC were observed between the young and the elderly subjects for both the parent drug and the metabolite."( The effects of age and renal and hepatic impairment on the pharmacokinetics of sildenafil.
Colburn, W; Haug-Pihale, G; Muirhead, GJ; Rouviex, B; Wilner, K, 2002
)
"To examine the effect of concomitant cimetidine or antacid administration on the pharmacokinetic profile of sildenafil citrate in healthy male volunteers in two open-label, randomized studies."( The effects of cimetidine and antacid on the pharmacokinetic profile of sildenafil citrate in healthy male volunteers.
Laboy, L; LeBel, M; Wilner, K, 2002
)
"Coadministration of cimetidine had no statistically significant effect on the tmax or kel of sildenafil but caused a statistically significant increase in sildenafil AUCt and Cmax of 56% and 54%, respectively (P<0."( The effects of cimetidine and antacid on the pharmacokinetic profile of sildenafil citrate in healthy male volunteers.
Laboy, L; LeBel, M; Wilner, K, 2002
)
" Antacid coadministration had no effect on the pharmacokinetic profile of sildenafil."( The effects of cimetidine and antacid on the pharmacokinetic profile of sildenafil citrate in healthy male volunteers.
Laboy, L; LeBel, M; Wilner, K, 2002
)
"Repeated dosing with erythromycin caused statistically significant increases in the AUC and Cmax of sildenafil (2."( The effects of steady-state erythromycin and azithromycin on the pharmacokinetics of sildenafil in healthy volunteers.
Faulkner, S; Harness, JA; Muirhead, GJ; Taubel, J, 2002
)
" Under the nonfasting regimen, the Cmax central value was more than 4-fold and the AUC(infinity) central value more than 2-fold the central value of the fasting regimen."( Effect of food on the pharmacokinetics of fiduxosin in healthy male subjects.
Dutta, S; Granneman, GR; Verlinden, M; Zhang, Y,
)
"The response to regimens including lopinavir-ritonavir (LPV/r) in patients who have received multiple protease (PR) inhibitors (PI) can be analyzed in terms of human immunodeficiency virus type 1 (HIV-1) genotypic and pharmacokinetic (pK) determinants."( Human immunodeficiency virus type 1 genotypic and pharmacokinetic determinants of the virological response to lopinavir-ritonavir-containing therapy in protease inhibitor-experienced patients.
Breilh, D; Dabis, F; Dupon, M; Fleury, H; Lavignolle, V; Lawson-Ayayi, S; Masquelier, B; Morlat, P; Neau, D; Ragnaud, JM, 2002
)
" Pharmacokinetic curves were obtained for lopinavir and saquinavir."( Lopinavir/ritonavir plus saquinavir in salvage therapy; pharmacokinetics, tolerability and efficacy.
Burger, DM; la Porte, CJ; Rockstroh, JK; Schneider, K; Wasmuth, JC, 2003
)
"To evaluate the pharmacokinetic and pharmacodynamic characteristics of YH1885, a novel proton pump inhibitor, a single-blind, randomized, placebo-controlled, dose-rising, parallel-group study was conducted in 46 healthy volunteers."( Pharmacokinetic and pharmacodynamic evaluation of a novel proton pump inhibitor, YH1885, in healthy volunteers.
Bae, KS; Cho, JY; Chung, JY; Jang, IJ; Lim, HS; Moon, BS; Shin, SG; Shon, JH; Song, KS; Yi, SY; Yu, KS, 2004
)
"The pharmacokinetic parameters of lopinavir (LPV) were examined by administering Kaletra (LPV+ritonavir) to 8 healthy Japanese volunteers both in the fasting and postprandial conditions."( Pharmacokinetics of lopinavir after administration of Kaletra in healthy Japanese volunteers.
Ito, H; Kaneda, T; Mamiya, N; Nagaoka, K; Nakai, M; Oki, T; Sagisaka, M; Usami, Y; Utsumi, M; Yamanaka, K, 2004
)
" Patients receiving the same doses of lopinavir/ritonavir (n = 10) or amprenavir with ritonavir (n = 8) were chosen as controls for pharmacokinetic analyses."( Deep salvage with amprenavir and lopinavir/ritonavir: correlation of pharmacokinetics and drug resistance with pharmacodynamics.
Baldini, F; Cauda, R; Cingolani, A; De Luca, A; Di Giambenedetto, S; Hoetelmans, RM, 2004
)
"Coadministration of lopinavir-ritonavir, an antiretroviral protease inhibitor, at the standard dose (400/100 mg twice a day [BID]) with the antituberculous agent rifampin is contraindicated because of a significant pharmacokinetic interaction due to induction of cytochrome P450 3A by rifampin."( Pharmacokinetics of adjusted-dose lopinavir-ritonavir combined with rifampin in healthy volunteers.
Bertz, R; Boeree, MJ; Burger, DM; Colbers, EP; Hekster, YA; Koopmans, PP; la Porte, CJ; Voncken, DS; Wikstrom, K, 2004
)
"The main purpose of the present review article was to shed light on the different 5-fluorouracil (5-FU) prodrugs by underlining their respective pharmacological features in terms of metabolic activation, dihydropyrimidine dehydrogenase inhibition, pharmacokinetic profile and biomodulation ability."( Comparative pharmacology of oral fluoropyrimidines: a focus on pharmacokinetics, pharmacodynamics and pharmacomodulation.
Ferrero, JM; François, E; Milano, G, 2004
)
" The median pharmacokinetic parameters of lopinavir were as follows: area under the concentration-time curve from 0 to 12 h (AUC(0-12)), 85."( Steady-state pharmacokinetics of a double-boosting regimen of saquinavir soft gel plus lopinavir plus minidose ritonavir in human immunodeficiency virus-infected adults.
Azuaje, C; Clotet, B; Crespo, M; Diaz, M; Falcó, V; Lopez, RM; Ocaña, I; Pahissa, A; Pou, L; Ribera, E; Ruiz, I; Ruiz, L, 2004
)
" In contrast, the sparse sampling done in population pharmacokinetic studies relies on patient-reported times of dosing, the accuracy of which the authors sought to assess by adding electronic monitoring to the usual patient reporting of dosing times."( Successful projection of the time course of drug concentration in plasma during a 1-year period from electronically compiled dosing-time data used as input to individually parameterized pharmacokinetic models.
Bertz, R; Mayer, S; Rode, R; Tousset, E; Urquhart, J; Vrijens, B, 2005
)
" LPV/r concentrations were measured by LC-MS/MS, and the data were analyzed by noncompartmental pharmacokinetic analysis."( Absence of circadian variation in the pharmacokinetics of lopinavir/ritonavir given as a once daily dosing regimen in HIV-1-infected patients.
Bourbeau, M; Cameron, DW; Garber, GE; Giguere, P; Seguin, I; van Heeswijk, RP, 2005
)
" This was the first clinical study in humans to demonstrate the plasma pharmacokinetics and the pharmacodynamic effectiveness of the PNP inhibitor, forodesine; however, regrowth of leukemia cells in the blood and marrow after course 1 suggested that a different therapeutic schedule should be considered for future studies."( A proof-of-principle pharmacokinetic, pharmacodynamic, and clinical study with purine nucleoside phosphorylase inhibitor immucillin-H (BCX-1777, forodesine).
Ayres, M; Bantia, S; Davisson, J; Du, M; Faderl, S; Gandhi, V; Harman, L; Kantarjian, H; Kilpatrick, JM; Plunkett, W; Thomas, D; Wierda, WG, 2005
)
"To develop a population pharmacokinetic model for lopinavir in combination with ritonavir, in which the interaction between both drugs was characterized, and in which relationships between patient characteristics and pharmacokinetics were identified."( Population pharmacokinetics of lopinavir in combination with ritonavir in HIV-1-infected patients.
Beijnen, JH; Crommentuyn, KM; Huitema, AD; Kappelhoff, BS; Mairuhu, AT; Meenhorst, PL; Mulder, JW; van Gorp, EC, 2005
)
" First, ritonavir data were fitted to a previously developed model to obtain individual Bayesian estimates of pharmacokinetic parameters."( Population pharmacokinetics of lopinavir in combination with ritonavir in HIV-1-infected patients.
Beijnen, JH; Crommentuyn, KM; Huitema, AD; Kappelhoff, BS; Mairuhu, AT; Meenhorst, PL; Mulder, JW; van Gorp, EC, 2005
)
"We have developed a model that has defined a time-independent inverse relationship between the exposure to ritonavir and the CL/F of lopinavir, and provided an adequate description of the pharmacokinetic parameters for the latter."( Population pharmacokinetics of lopinavir in combination with ritonavir in HIV-1-infected patients.
Beijnen, JH; Crommentuyn, KM; Huitema, AD; Kappelhoff, BS; Mairuhu, AT; Meenhorst, PL; Mulder, JW; van Gorp, EC, 2005
)
"Samples were collected for a 12-hour pharmacokinetic profile in all children."( Pharmacokinetics and 24-week efficacy/safety of dual boosted saquinavir/lopinavir/ritonavir in nucleoside-pretreated children.
Ananworanich, J; Bergshoeff, A; Burger, D; Engchanil, C; Hill, A; Kosalaraksa, P; Pancharoen, C; Ruxrungtham, K; Siangphoe, U, 2005
)
" Median area under the concentration curve at 0-12 hours and Cmin were 39."( Pharmacokinetics and 24-week efficacy/safety of dual boosted saquinavir/lopinavir/ritonavir in nucleoside-pretreated children.
Ananworanich, J; Bergshoeff, A; Burger, D; Engchanil, C; Hill, A; Kosalaraksa, P; Pancharoen, C; Ruxrungtham, K; Siangphoe, U, 2005
)
"Six HIV-positive antiretroviral experienced patients initiating therapy with a regimen including lopinavir/ritonavir (400/100 mg twice per day) and indinavir (800 mg twice per day) underwent steady-state pharmacokinetic analysis."( Steady-state pharmacokinetics and tolerability of indinavir-lopinavir/r combination therapy in antiretroviral-experienced patients.
Antoniou, T; Giguere, P; Phillips, EJ; Tseng, AL; van Heeswijk, RP; Walker, SE, 2005
)
"The influence of saquinavir hard-gel capsules on lopinavir pharmacokinetic parameters was investigated using a population approach."( No significant influence of saquinavir hard-gel capsule administration on pharmacokinetics of lopinavir in combination with ritonavir: a population approach.
Allavena, C; Dailly, E; Gagnieu, MC; Jolliet, P; Raffi, F, 2005
)
" When the 2 hepatic impairment groups were combined, lopinavir Cmax and AUC12 were increased 20% to 30% compared to the controls."( Pharmacokinetics of lopinavir/ritonavir in HIV/hepatitis C virus-coinfected subjects with hepatic impairment.
Arribas, J; Brun, SC; Causemaker, SJ; Cepeda, C; DaSilva, B; García Cabanillas, JA; Li, J; Lorenzo, A; Peng, JZ; Pulido, F, 2006
)
" Oral absorption of telbivudine as measured by maximum plasma concentration (Cmax), time to reach Cmax (Tmax), and area under the plasma concentration-time curve (AUC(0-t) and AUC(0-infinity)) was not altered by food intake immediately before oral dosing."( Absence of food effect on the pharmacokinetics of telbivudine following oral administration in healthy subjects.
Brown, NA; Chao, GC; Lloyd, DM; Zhou, XJ, 2006
)
" Pharmacokinetic and pharmacodynamic analyses by using maximum-effect modeling established a quantitative relationship between a reduction in serum HBV DNA levels and parameters of drug exposure, in particular, the steady-state C(max) and AUC(0-t)."( Pharmacokinetics of telbivudine following oral administration of escalating single and multiple doses in patients with chronic hepatitis B virus infection: pharmacodynamic implications.
Brown, NA; Chao, GC; Lai, CL; Lim, SG; Lloyd, DM; Zhou, XJ, 2006
)
"To assess potential pharmacokinetic (PK) interactions between atazanavir (ATV, 300 mg, once daily) and lopinavir (LPV, 400 mg, twice daily), both boosted by ritonavir (RTV, 100 mg)."( Ritonavir-boosted atazanavir-lopinavir combination: a pharmacokinetic interaction study of total, unbound plasma and cellular exposures.
Biollaz, J; Buclin, T; Cavassini, M; Colombo, S; Decosterd, LA; Franc, C; Guignard, N; Khonkarly, M; Rochat, B; Tarr, PE; Telenti, A, 2006
)
" The subjects were administered a single oral dose of 600 mg telbivudine, and blood samples were collected over a 48-h interval for pharmacokinetic analyses."( Pharmacokinetics of telbivudine in subjects with various degrees of hepatic impairment.
Alcorn, HW; Brown, NA; Chao, GC; Dubuc Patrick, G; Marbury, TC; Smith, WB; Zhou, XJ, 2006
)
" Minimum and maximum concentrations (C subsetmin, C subsetmax), area under the concentration-time curve (AUC subset0-12h), total clearance (CL subsettot) and half-life (t1/2) were calculated."( Pharmacokinetics and tolerability of a combination of indinavir, lopinavir and ritonavir in multiply pretreated HIV-1 infected adults.
Harder, S; Klauke, S; Kurowski, M; Lutz, T; Müller, A; Rottmann, C; Staszewski, S; von Hentig, N, 2006
)
" 3,467 ng*h/mL; Cmin 220 ng/mL vs."( Pharmacokinetics and tolerability of a combination of indinavir, lopinavir and ritonavir in multiply pretreated HIV-1 infected adults.
Harder, S; Klauke, S; Kurowski, M; Lutz, T; Müller, A; Rottmann, C; Staszewski, S; von Hentig, N, 2006
)
" The mean (standard deviation) AUC0-24, Cmax and Cmin of lopinavir were 149."( Pharmacokinetics of a once-daily regimen of lopinavir/ritonavir in HIV-1-infected children.
Burger, D; de Groot, R; van der Lee, M; Verweel, G, 2006
)
"Our findings indicate that 460/115 mg/m2 lopinavir/ritonavir once daily leads to mean pharmacokinetic parameters comparable to data of 800/200 mg lopinavir/ritonavir once daily in adults, although the variability observed in the trough levels is much higher in children."( Pharmacokinetics of a once-daily regimen of lopinavir/ritonavir in HIV-1-infected children.
Burger, D; de Groot, R; van der Lee, M; Verweel, G, 2006
)
" Pharmacokinetic sampling was performed on day 8 of each treatment, and samples were analyzed for FPV, amprenavir (APV), LPV, and RTV concentrations by high-performance liquid chromatography-tandem mass spectrometry."( Dose separation does not overcome the pharmacokinetic interaction between fosamprenavir and lopinavir/ritonavir.
Corbett, AH; Eron, JJ; Kalvass, LA; Kashuba, AD; Lim, ML; Ngo, LT; Patterson, KB; Tien, HC, 2006
)
"5 hours, plasma disposition of the drug was biphasic with a mean terminal half-life ranging from 39."( Single-dose and multiple-dose pharmacokinetics and safety of telbivudine after oral administration in healthy Chinese subjects.
Brown, NA; Chao, GC; Hu, P; Jiang, J; Pietropaolo, K; Wang, H; Zhou, XJ, 2006
)
" A pre-dose to 6 h post-dose steady-state pharmacokinetic analysis (n = 35) of the drugs on the day of the scheduled Caesarean section was performed."( Placental transfer and pharmacokinetics of lopinavir and other protease inhibitors in combination with nevirapine at delivery.
Belohradsky, BH; Eberle, J; Friese, K; Gingelmaier, A; Grubert, TA; Kästner, R; Kurowski, M; Mylonas, I, 2006
)
" The consequences of these pharmacokinetic discrepancies and the necessity to modify the currently recommended dosage regimen should be further investigated."( Population analysis of weight-, age-, and sex-related differences in the pharmacokinetics of lopinavir in children from birth to 18 years.
Blanche, S; Chaix, ML; Delaugerre, C; Firtion, G; Hirt, D; Jullien, V; Macassa, E; Pons, G; Rey, E; Rouzioux, C; Teglas, JP; Tréluyer, JM; Urien, S; Vaz, P, 2006
)
"To evaluate the pharmacokinetic profile of telbivudine in healthy Chinese subjects after oral administration of single and multiple doses."( [Study on the pharmacokinetic profile of telbivudine].
Brown, NA; Hu, P; Jiang, J; Shen, K; Wang, HY; Zhou, XJ, 2006
)
" Pharmacokinetic parameters were calculated by using the non-compartmental approach."( [Study on the pharmacokinetic profile of telbivudine].
Brown, NA; Hu, P; Jiang, J; Shen, K; Wang, HY; Zhou, XJ, 2006
)
" The optimization of physicochemical properties, pharmacokinetic profiles, and potency led to the identification of 13 in the dihydroxypyrimidine series and 18 in the N-methylpyrimidinone series having low nanomolar activity in the cellular HIV spread assay in the presence of 50% normal human serum and very good pharmacokinetics in preclinical species."( 4,5-dihydroxypyrimidine carboxamides and N-alkyl-5-hydroxypyrimidinone carboxamides are potent, selective HIV integrase inhibitors with good pharmacokinetic profiles in preclinical species.
Gardelli, C; Laufer, R; Matassa, VG; Monteagudo, E; Muraglia, E; Pace, P; Paz, OG; Petrocchi, A; Rowley, M; Summa, V, 2006
)
" Thus, for ritonavir AUC12, Cmax and Cmin in HCV+/FIB+patients were 63%, 86% and 100% higher, respectively, when compared with those parameters in HCV-patients (p=0."( Lopinavir/ritonavir pharmacokinetics in HIV and hepatitis C virus co-infected patients without liver function impairment: influence of liver fibrosis.
Barbanoj, MJ; Blanco, A; Clotet, B; Costa, J; DelaVarga, M; Domingo, P; Miranda, C; Miranda, J; Moltó, J; Negredo, E; Tural, C; Valle, M; Vilaró, J, 2007
)
" Lopinavir and ritonavir pharmacokinetic parameters were evaluated."( Lack of effect of gastric acid-reducing agents on the pharmacokinetics of lopinavir/ritonavir in HIV-infected patients.
Awni, W; Brun, S; Chiu, YL; King, KR; Klein, CE; Naylor, C; Woodward, WC, 2007
)
" Pharmacokinetic parameters estimated by noncompartmental method were reported as 90% confidence intervals (CIs) about the geometric mean ratio (GMR)."( Lopinavir/Ritonavir pharmacokinetic profile: impact of sex and other covariates following a change from twice-daily to once-daily therapy.
Acosta, EP; Binongo, JN; Chuck, SK; Lennox, JL; Ofotokun, I; Palau, M, 2007
)
"To investigate the pharmacokinetic profile and tissue distribution of a novel phosphodiesterase type 5 inhibitor, 5-ethyl-2-{5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-2-propoxy-phenyl}-7-propyl-3,5-dihydro-pyrrolo(3,2-d)pyrimidin-4-one (SK-3530), in rats after administration of the (14)C-labeled compound."( Pharmacokinetics and tissue distribution of a novel PDE5 inhibitor, SK-3530, in rats.
Im, GJ; Kim, DH; Kim, NS; Yoo, HH, 2007
)
"The pharmacokinetic parameters of SK-3530 were measured based on the total radioactivity and parent SK-3530 concentration in rat plasma after intravenous and oral administration."( Pharmacokinetics and tissue distribution of a novel PDE5 inhibitor, SK-3530, in rats.
Im, GJ; Kim, DH; Kim, NS; Yoo, HH, 2007
)
" The developed assay was applied to a clinical pharmacokinetic study after oral administration of SK3530 in healthy male volunteers (dose 100 mg)."( Development of LC/MS/MS assay for the determination of 5-ethyl-2-{5-[4-(2-hydroxyethyl)piperazine-1-sulfonyl]-2-propoxyphenyl}-7-propyl-3,5-dihydropyrrolo[3,2-d]pyrimidin-4-one (SK3530) in human plasma: application to a clinical pharmacokinetic study.
Hu, SK; Kim, DK; Kim, J; Lee, B; Lee, JY; Oh, JG; Shin, BS; Um, KA; Yoo, SD; Youn, WN, 2007
)
"HIV-infected subjects on abacavir (600 mg once daily) plus two nucleoside reverse transcriptase inhibitors (NRTIs) (excluding tenofovir) underwent a 24 h pharmacokinetic assessment for plasma abacavir concentrations."( Abacavir plasma pharmacokinetics in the absence and presence of atazanavir/ritonavir or lopinavir/ritonavir and vice versa in HIV-infected patients.
Back, D; Boffito, M; Bonora, S; D'Avolio, A; Else, L; Gazzard, B; Mandalia, S; Moyle, G; Nelson, M; Pozniak, A; Waters, LJ, 2007
)
" The clinical consequences of these substantial pharmacokinetic changes should be investigated."( Lopinavir-ritonavir dramatically affects the pharmacokinetics of irinotecan in HIV patients with Kaposi's sarcoma.
Corona, G; Innocenti, F; Sandron, S; Sartor, I; Tirelli, U; Toffoli, G; Vaccher, E, 2008
)
" Subjects received a single oral dose of telbivudine at 600 mg (normal function and mild impairment), 400 mg (moderate impairment), or 200 mg (severe impairment and ESRD); plasma and/or urine samples were collected over a 48-h period for pharmacokinetic analyses."( Pharmacokinetics of telbivudine in subjects with various degrees of renal impairment.
Brown, NA; Chao, GC; Dubuc-Patrick, G; Marbury, TC; Smith, WB; Swan, S; Zhou, XJ, 2007
)
" Data originated from pre-defined pharmacokinetic substudies within two randomized 48-week trials evaluating the safety and efficacy of three protease inhibitor regimens."( Pharmacokinetics of two randomized trials evaluating the safety and efficacy of indinavir, saquinavir and lopinavir in combination with low-dose ritonavir: the MaxCmin1 and 2 trials.
Cahn, P; Castagna, A; Clumeck, N; Dragsted, UB; Fox, Z; Gerstoft, J; Justesen, US; Losso, M; Lundgren, JD; Obel, N; Pedersen, C; Peters, B, 2007
)
"Fourteen patients participated in the study and seven participated in the intensified pharmacokinetic protocol."( Effect of highly active antiretroviral therapy on tacrolimus pharmacokinetics in hepatitis C virus and HIV co-infected liver transplant recipients in the ANRS HC-08 study.
Abbara, C; Barrail, A; Boissonnas, A; Bonhomme-Faivre, L; Duclos-Vallée, JC; Samuel, D; Taburet, AM; Teicher, E; Vincent, I; Vittecoq, D, 2007
)
" Coadministration of these drugs might result in complex pharmacokinetic drug-drug interactions."( Amprenavir and lopinavir pharmacokinetics following coadministration of amprenavir or fosamprenavir with lopinavir/ritonavir, with or without efavirenz.
Barditch-Crovo, P; Carson, KA; Flexner, C; Hendrix, CW; Khan, W; Pakes, GE; Parish, M; Parsons, T; Pham, PA; Qaqish, R; Radebaugh, C, 2007
)
"37) or Cmax (10."( Amprenavir and lopinavir pharmacokinetics following coadministration of amprenavir or fosamprenavir with lopinavir/ritonavir, with or without efavirenz.
Barditch-Crovo, P; Carson, KA; Flexner, C; Hendrix, CW; Khan, W; Pakes, GE; Parish, M; Parsons, T; Pham, PA; Qaqish, R; Radebaugh, C, 2007
)
"EFV did not appear to significantly alter APV and LPV pharmacokinetic parameters in HIV-infected patients taking APV 750 mg twice daily + LPV 533/133 mg twice daily."( Amprenavir and lopinavir pharmacokinetics following coadministration of amprenavir or fosamprenavir with lopinavir/ritonavir, with or without efavirenz.
Barditch-Crovo, P; Carson, KA; Flexner, C; Hendrix, CW; Khan, W; Pakes, GE; Parish, M; Parsons, T; Pham, PA; Qaqish, R; Radebaugh, C, 2007
)
" Intensive pharmacokinetic sampling was performed at 2 weeks and predose concentrations were collected every 8 weeks; safety and plasma HIV-1 RNA were monitored every 4-12 weeks for 24 weeks."( Pharmacokinetics, safety and efficacy of lopinavir/ritonavir in infants less than 6 months of age: 24 week results.
Capparelli, EV; Chadwick, EG; Chen, J; Hughes, M; Palumbo, P; Pinto, JA; Robbins, B; Rodman, JH; Serchuck, L; Smith, E; Yogev, R, 2008
)
" Lopinavir pharmacokinetic measures (median [interquartile range]) for children with and without rifampicin, respectively, were maximum concentration (Cmax) of 10."( Effect of rifampicin on lopinavir pharmacokinetics in HIV-infected children with tuberculosis.
Egbers, C; Eley, BS; Maartens, G; McIlleron, HM; Meyers, TM; Nuttall, JJ; Ren, Y; Smith, PJ, 2008
)
" Although the median Cmax and AUC0-12 were lowered by 26% and 31%."( Effect of rifampicin on lopinavir pharmacokinetics in HIV-infected children with tuberculosis.
Egbers, C; Eley, BS; Maartens, G; McIlleron, HM; Meyers, TM; Nuttall, JJ; Ren, Y; Smith, PJ, 2008
)
"Studies on the pharmacokinetic interaction between atazanavir and lopinavir with ritonavir (lopinavir/ritonavir) report contradictory results."( Atazanavir and lopinavir with ritonavir alone or in combination: analysis of pharmacokinetic interaction and predictors of drug exposure.
Bacarelli, A; Cauda, R; De Luca, A; Di Giambenedetto, S; Navarra, P; Ragazzoni, E; Regazzi, M; Villani, P, 2008
)
" The method was successfully applied to a preclinical pharmacokinetic study of yonkenafil in rat after sublingual, oral and intravenous administration."( A rapid and sensitive LC-MS/MS assay to quantify yonkenafil in rat plasma with application to preclinical pharmacokinetics studies.
Fawcett, JP; Gu, J; Jiang, Y; Kong, J; Tang, Y; Teng, G; Wang, J; Wang, Y, 2008
)
" Total (n = 56) and unbound (n = 36) LPV pharmacokinetic parameters were determined at steady-state using validated high-performance liquid chromatography with ultraviolet detection and high-performance liquid chromatography-tandem mass spectrometry methods, respectively."( Lopinavir/ritonavir pharmacokinetics in HIV/HCV-coinfected patients with or without cirrhosis.
Back, DJ; Cargnel, A; Cordier, L; Cusato, M; Dickinson, L; Duca, P; Khoo, SH; Meraviglia, P; Micheli, V; Orlando, G; Regazzi, M; Rizzardini, G; Viganò, P; Villani, P, 2008
)
" It is coformulated with low doses of ritonavir in order to enhance its pharmacokinetic profile."( Simultaneous population pharmacokinetic model for lopinavir and ritonavir in HIV-infected adults.
Barbanoj, MJ; Blanco, A; Clotet, B; Costa, J; Domingo, P; Miranda, C; Moltó, J; Negredo, E; Santos, JR; Valle, M, 2008
)
"To develop and validate a population pharmacokinetic model for lopinavir and ritonavir administered simultaneously in a population of HIV-infected adults."( Simultaneous population pharmacokinetic model for lopinavir and ritonavir in HIV-infected adults.
Barbanoj, MJ; Blanco, A; Clotet, B; Costa, J; Domingo, P; Miranda, C; Moltó, J; Negredo, E; Santos, JR; Valle, M, 2008
)
" First, a population pharmacokinetic model was developed for lopinavir and for ritonavir separately."( Simultaneous population pharmacokinetic model for lopinavir and ritonavir in HIV-infected adults.
Barbanoj, MJ; Blanco, A; Clotet, B; Costa, J; Domingo, P; Miranda, C; Moltó, J; Negredo, E; Santos, JR; Valle, M, 2008
)
" LPV Cmin was lower than expected in the hemodialysis group."( The pharmacokinetics and pharmacogenomics of efavirenz and lopinavir/ritonavir in HIV-infected persons requiring hemodialysis.
Amorosa, V; Cramer, YS; Gupta, SK; Hall, SD; Koletar, SL; Rosenkranz, SL; Szczech, LA, 2008
)
" A mixed-effects pharmacokinetic model that included two-compartment disposition of sildenafil and its metabolite and an effect of postnatal age on sildenafil clearance was used to describe plasma concentration-time data of parent and metabolite."( Population pharmacokinetics of sildenafil in term neonates: evidence of rapid maturation of metabolic clearance in the early postnatal period.
Dombi, T; Lalonde, R; Mukherjee, A; Wittke, B, 2009
)
"This was an open-label, three-session, pharmacokinetic trial."( Pharmacokinetics of atazanavir/ritonavir once daily and lopinavir/ritonavir twice and once daily over 72 h following drug cessation.
Back, D; Boffito, M; Else, L; Gazzard, B; Khoo, S; Moyle, G; Pozniak, A; Sousa, M; Taylor, J, 2008
)
"This study investigated the pharmacokinetic forgiveness of two boosted protease inhibitors."( Pharmacokinetics of atazanavir/ritonavir once daily and lopinavir/ritonavir twice and once daily over 72 h following drug cessation.
Back, D; Boffito, M; Else, L; Gazzard, B; Khoo, S; Moyle, G; Pozniak, A; Sousa, M; Taylor, J, 2008
)
" However, the sequential metabolism of M2, nonlinear AMG 487 pharmacokinetics, and the inability to accurately determine the role of intestinal AMG 487 metabolism complicates the correlation between M2 plasma concentrations and the time-dependent AMG 487 pharmacokinetic changes."( An inhibitory metabolite leads to dose- and time-dependent pharmacokinetics of (R)-N-{1-[3-(4-ethoxy-phenyl)-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-yl]-ethyl}-N-pyridin-3-yl-methyl-2-(4-trifluoromethoxy-phenyl)-acetamide (AMG 487) in human subjects af
Berry, K; Cho, R; Floren, LC; Johnson, MG; Kersey, K; Ma, J; Marcus, AP; Medina, JC; Pearson, PG; Tonn, GR; Van Lengerich, B; Wang, X; Wong, BK; Wong, SC; Wong, SG, 2009
)
" The aims of this study were to develop a population pharmacokinetic (PK) model of LPV in children and to estimate the probability of achieving a PIQ of >15."( Population pharmacokinetics of lopinavir predict suboptimal therapeutic concentrations in treatment-experienced human immunodeficiency virus-infected children.
Baghdassarian, A; Neely, MN; Rakhmanina, N; Soldin, S; van den Anker, J; Williams, K, 2009
)
" Statistical analyses were performed on pharmacokinetic parameters: the area under the concentration-time curve from 0 to 4 h (AUC(0-4)), the maximum concentration of the drug (C(max)), and the residual concentration of the drug at the end of the dosing interval (C(trough)) for plasma and the AUC(0-4) and C(trough) for intracellular data."( Pilot pharmacokinetic study of human immunodeficiency virus-infected patients receiving tenofovir disoproxil fumarate (TDF): investigation of systemic and intracellular interactions between TDF and abacavir, lamivudine, or lopinavir-ritonavir.
Ayen, R; Clotet, B; Grassi, J; Levi, M; Negredo, E; Pruvost, A; Puig, J; Théodoro, F, 2009
)
" A population pharmacokinetic model was developed based on data pooled from 16 early phase studies in 363 healthy participants and patients."( Population pharmacokinetics of telbivudine and determination of dose adjustment for patients with renal impairment.
Farrell, C; Ke, J; Mayers, DL; Pentikis, HS; Sallas, WM; Zhou, XJ, 2009
)
" For artemether, trends toward Cmax and AUC decreases (Cmax 14."( Lopinavir/ritonavir affects pharmacokinetic exposure of artemether/lumefantrine in HIV-uninfected healthy volunteers.
Aweeka, FT; Charlebois, E; Dorsey, G; German, P; Hanpithakpong, W; Havlir, D; Lawrence, J; Lindegardh, N; Parikh, S; Rosenthal, PJ, 2009
)
" Full pharmacokinetic profiles were analysed for lopinavir and ritonavir with a validated HPLC tandem mass spectrometry assay."( Pharmacokinetics and tolerability of once- versus twice-daily lopinavir/ritonavir treatment in HIV-1-infected children.
la Porte, C; Mitchell, CD; Parker, J; Rongkavilit, C; van Heeswijk, R; Zhang, G, 2009
)
"This study assessed the hemodynamic effects and pharmacokinetic properties of mirodenafil administered with alcohol."( Influence of alcohol on the hemodynamic effects and pharmacokinetic properties of mirodenafil: a single-dose, randomized-sequence, open-label, crossover study in healthy male volunteers in Korea.
Jang, IJ; Kim, BH; Kim, J; Kim, KP; Lee, B; Lim, KS; Shin, SG; Yi, S; Yu, KS, 2009
)
" Pharmacokinetic parameters of mirodenafil were not significantly different when the drug was administered with or without alcohol."( Influence of alcohol on the hemodynamic effects and pharmacokinetic properties of mirodenafil: a single-dose, randomized-sequence, open-label, crossover study in healthy male volunteers in Korea.
Jang, IJ; Kim, BH; Kim, J; Kim, KP; Lee, B; Lim, KS; Shin, SG; Yi, S; Yu, KS, 2009
)
" A 12 h pharmacokinetic study was done at 4-6 weeks after starting treatment."( Pharmacokinetics and 48 week efficacy of low-dose lopinavir/ritonavir in HIV-infected children.
Ananworanich, J; Boonrak, P; Bunupuradah, T; Burger, D; Gorowara, M; Jupimai, T; Pancharoen, C; Phasomsap, C; Puthanakit, T; Ruxrungtham, K; van der Lugt, J, 2009
)
"Low-dose lopinavir displayed adequate pharmacokinetic parameters and good efficacy as compared with standard-dose lopinavir in Thai children."( Pharmacokinetics and 48 week efficacy of low-dose lopinavir/ritonavir in HIV-infected children.
Ananworanich, J; Boonrak, P; Bunupuradah, T; Burger, D; Gorowara, M; Jupimai, T; Pancharoen, C; Phasomsap, C; Puthanakit, T; Ruxrungtham, K; van der Lugt, J, 2009
)
" Noncompartmental and population pharmacokinetic analyses (2-compartment open model) were performed."( Pharmacokinetic evaluation of rifabutin in combination with lopinavir-ritonavir in patients with HIV infection and active tuberculosis.
Ashkin, D; Boulanger, C; Espinoza, LA; Farrell, K; Graham, JJ; Hollender, E; Maasen, D; Peloquin, CA; Rivero, RO; Stambaugh, JJ; Symes, S, 2009
)
" For the five pharmacokinetic trials of lopinavir/ritonavir, a meta-analysis was used to estimate the effects of lopinavir dose versus ritonavir dose on lopinavir pharmacokinetics."( How much ritonavir is needed to boost protease inhibitors? Systematic review of 17 dose-ranging pharmacokinetic trials.
Boffito, M; Hill, A; Sawyer, W; van der Lugt, J, 2009
)
"The pharmacokinetic parameters of mirodenafil and SK3541 (a metabolite of mirodenafil) were compared after the intravenous and oral administration of mirodenafil at a dose of 20 mg/kg to U-ARF and control rats."( Faster clearance of mirodenafil in rats with acute renal failure induced by uranyl nitrate: contribution of increased protein expression of hepatic CYP3A1 and intestinal CYP1A1 and 3A1/2.
Choi, YH; Kim, TK; Lee, BY; Lee, MG; Lee, YS, 2009
)
"A population pharmacokinetic model for lopinavir was developed using data from 424 HIV type-1-infected patients, and the final model was used to estimate the probability to achieve target C(troughs) via Monte Carlo simulations."( A population analysis of weight-related differences in lopinavir pharmacokinetics and possible consequences for protease inhibitor-naive and -experienced patients.
Bouillon-Pichault, M; Chhun, S; Dupin, N; Jullien, V; Krivine, A; Launay, O; Lortholary, O; Morini, JP; Piketty, C; Pons, G; Salmon, D; Treluyer, JM; Viard, JP; Weiss, L, 2009
)
"To determine the pharmacokinetic profiles of lopinavir and ritonavir in two newly developed generic co-formulations for HIV-infected children (Lopimune paediatric tablets and granules, 100/25 mg of lopinavir/ritonavir, Cipla Pharmaceuticals), and to compare these with the branded product (Kaletra)."( Pharmacokinetics of two generic co-formulations of lopinavir/ritonavir for HIV-infected children: a pilot study of paediatric Lopimune versus the branded product in healthy adult volunteers.
Burger, DM; Colbers, EP; de Kanter, CT; Fillekes, Q; Hoitsma, A, 2010
)
" A 32 h pharmacokinetic curve was recorded."( Pharmacokinetics of two generic co-formulations of lopinavir/ritonavir for HIV-infected children: a pilot study of paediatric Lopimune versus the branded product in healthy adult volunteers.
Burger, DM; Colbers, EP; de Kanter, CT; Fillekes, Q; Hoitsma, A, 2010
)
"Large differences in pharmacokinetic parameters can be excluded for Lopimune paediatric tablets when compared with the branded product and taken on an empty stomach, and also for Lopimune granules when these are taken with food."( Pharmacokinetics of two generic co-formulations of lopinavir/ritonavir for HIV-infected children: a pilot study of paediatric Lopimune versus the branded product in healthy adult volunteers.
Burger, DM; Colbers, EP; de Kanter, CT; Fillekes, Q; Hoitsma, A, 2010
)
" Serial blood samples were collected for pharmacokinetic analysis after the administration of mirodenafil in each study period."( The effects of ketoconazole and rifampicin on the pharmacokinetics of mirodenafil in healthy Korean male volunteers: an open-label, one-sequence, three-period, three-treatment crossover study.
Cho, JY; Jang, IJ; Kim, BH; Kim, JW; Kim, TE; Shin, KH; Shin, SG; Yi, S; Yoon, SH; Yu, KS, 2009
)
"We aimed to investigate the extent of pharmacokinetic drug interactions between bosentan and a fixed combination of lopinavir/ritonavir."( Mutual pharmacokinetic interactions between bosentan and lopinavir/ritonavir in healthy participants.
Dingemanse, J; Nilsson, PN; Patat, A; van Giersbergen, PL, 2010
)
" Six-point pharmacokinetic sampling (0, 2, 4, 6, 8, and 12 h) was undertaken after observed intake with a standardized breakfast."( Pharmacokinetics of lopinavir-ritonavir with and without nonnucleoside reverse transcriptase inhibitors in Ugandan HIV-infected adults.
Dickinson, L; Gibb, DM; Gilks, CF; Kayiwa, J; Khoo, S; Kityo, C; Lutwama, F; Munderi, P; Nalumenya, R; Reid, A; Ssali, F; Tumukunde, D; Walker, AS, 2010
)
" Forodesine has biologic activity in CLL; pharmacodynamic parameters suggest that an alternate dosing schedule and/or higher doses to achieve greater intracellular dGTP may be beneficial in this patient population."( Phase 2 and pharmacodynamic study of oral forodesine in patients with advanced, fludarabine-treated chronic lymphocytic leukemia.
Balakrishnan, K; Bantia, S; Bickel, S; Chen, Y; Gandhi, V; Kantarjian, H; Keating, MJ; Kilpatrick, JM; O'Brien, S; Ravandi, F; Tyler, BF; Verma, D, 2010
)
" LPV/r pharmacokinetic parameters were calculated using noncompartmental analysis."( Pharmacokinetics and virologic response of zidovudine/lopinavir/ritonavir initiated during the third trimester of pregnancy.
Chirayus, S; Cressey, TR; Jourdain, G; Kongpanichkul, R; Lallemant, M; Ngo-Giang-Huong, N; Pattarakulwanich, S; Rawangban, B; Sabsanong, P; Varadisai, S; Voramongkol, N; Yuthavisuthi, P, 2010
)
" Geometric mean (90% confidence interval) LPV AUC, Cmax and Cmin were 64."( Pharmacokinetics and virologic response of zidovudine/lopinavir/ritonavir initiated during the third trimester of pregnancy.
Chirayus, S; Cressey, TR; Jourdain, G; Kongpanichkul, R; Lallemant, M; Ngo-Giang-Huong, N; Pattarakulwanich, S; Rawangban, B; Sabsanong, P; Varadisai, S; Voramongkol, N; Yuthavisuthi, P, 2010
)
"International Maternal Pediatric Adolescent AIDS Clinical Trials 1026s is a prospective nonblinded pharmacokinetic study in HIV-infected pregnant women, including a cohort receiving 2 lopinavir/ritonavir tablets (400 mg/100 mg) twice daily during the second trimester, 3 tablets (600 mg/150 mg) twice daily during the third trimester, and 2 tablets (400 mg/100 mg) twice daily post delivery through 2 weeks postpartum."( Lopinavir tablet pharmacokinetics with an increased dose during pregnancy.
Best, BM; Burchett, SK; Capparelli, EV; Hu, C; Li, H; Mirochnick, M; Read, JS; Rossi, SS; Smith, E; Stek, AM, 2010
)
"Steady-state 12-hour pharmacokinetic profiles were performed during pregnancy and at 2 weeks postpartum."( Lopinavir tablet pharmacokinetics with an increased dose during pregnancy.
Best, BM; Burchett, SK; Capparelli, EV; Hu, C; Li, H; Mirochnick, M; Read, JS; Rossi, SS; Smith, E; Stek, AM, 2010
)
"This study was conducted to examine the pharmacokinetic interactions between buprenorphine/naloxone (BUP/NLX) and lopinavir/ritonavir (LPV/r) in HIV-seronegative subjects chronically maintained on BUP/NLX."( Pharmacokinetic interactions between buprenorphine/naloxone and once-daily lopinavir/ritonavir.
Altice, FL; Andrews, L; Bruce, RD; Fang, WB; Friedland, GH; Lin, SN; Ma, Q; Moody, DE; Morse, GD, 2010
)
"This study was an open labeled pharmacokinetic study in twelve HIV-seronegative subjects stabilized on at least 3 weeks of BUP/NLX therapy."( Pharmacokinetic interactions between buprenorphine/naloxone and once-daily lopinavir/ritonavir.
Altice, FL; Andrews, L; Bruce, RD; Fang, WB; Friedland, GH; Lin, SN; Ma, Q; Moody, DE; Morse, GD, 2010
)
"2 ng*hr/mL) and Cmax (6."( Pharmacokinetic interactions between buprenorphine/naloxone and once-daily lopinavir/ritonavir.
Altice, FL; Andrews, L; Bruce, RD; Fang, WB; Friedland, GH; Lin, SN; Ma, Q; Moody, DE; Morse, GD, 2010
)
" Pharmacodynamic responses indicate that the altered norbuprenorphine clearance did not lead to opioid withdrawal."( Pharmacokinetic interactions between buprenorphine/naloxone and once-daily lopinavir/ritonavir.
Altice, FL; Andrews, L; Bruce, RD; Fang, WB; Friedland, GH; Lin, SN; Ma, Q; Moody, DE; Morse, GD, 2010
)
" Pharmacokinetic parameters were compared using the 400/100 mg twice daily dose as reference, by determining geometric mean ratios (GMRs) and 90% confidence intervals."( Pharmacokinetics of plasma lopinavir/ritonavir following the administration of 400/100 mg, 200/150 mg and 200/50 mg twice daily in HIV-negative volunteers.
Amin, J; Back, D; Boffito, M; Else, L; Emery, S; Gazzard, B; Hill, A; Jackson, A; Khoo, S; Lin, E; Morley, R; Puls, R, 2011
)
"These pharmacokinetic data show that therapeutic plasma concentrations of lopinavir can be achieved with 200/150 mg of lopinavir/ritonavir twice daily (one Meltrex tablet and one 100 mg ritonavir capsule twice daily)."( Pharmacokinetics of plasma lopinavir/ritonavir following the administration of 400/100 mg, 200/150 mg and 200/50 mg twice daily in HIV-negative volunteers.
Amin, J; Back, D; Boffito, M; Else, L; Emery, S; Gazzard, B; Hill, A; Jackson, A; Khoo, S; Lin, E; Morley, R; Puls, R, 2011
)
" In xenografted tumor models, GSK1120212 orally dosed once daily had a long circulating half-life and sustained suppression of p-ERK1/2 for more than 24 hours; GSK1120212 also reduced tumor Ki67, increased p27(Kip1/CDKN1B), and caused tumor growth inhibition in multiple tumor models."( GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition.
Annan, R; Bleam, MR; Erskine, S; Fisher, KE; Gilmartin, AG; Groy, A; Kulkarni, SG; Laquerre, SG; Minthorn, EA; Moss, KG; Rominger, CM; Sutton, D; Yang, J; Zappacosta, F, 2011
)
" Data were modeled first separately and then together by using individually predicted ritonavir pharmacokinetic parameters in the final lopinavir model."( Sequential population pharmacokinetic modeling of lopinavir and ritonavir in healthy volunteers and assessment of different dosing strategies.
Aarons, L; Back, D; Boffito, M; Davies, G; Dickinson, L; Else, L; Khoo, S; Moyle, G; Pozniak, A; von Hentig, N, 2011
)
" Physiologically based pharmacokinetic modeling strategies are commonly used in drug discovery and development."( Application of physiologically based pharmacokinetic modeling to understanding the clinical pharmacokinetics of UK-369,003.
Davis, J; Jones, HM; Watson, KJ, 2011
)
" Primary objectives were to determine the maximum tolerated dose (MTD) (part A), assess efficacy (part B) and determine the pharmacokinetic profile (parts A and B)."( Phase I/II multicenter study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD4877 in patients with refractory acute myeloid leukemia.
Altman, JK; Borthukar, G; Curt, GA; Faderl, S; Garcia-Manero, G; Huszar, D; Kadia, T; Kantarjian, HM; Li, J; Minden, M; Odenike, O; Osmukhina, A; Padmanabhan, S; Sankhala, K; Stock, W; Tallman, MS; Wu, K, 2012
)
" There were no significant differences in the LPV area under the plasma concentration-time curve from 0 to 12 h (AUC(0-12)), C(0), C(12), maximum concentration of drug in serum (C(max)), or half-life (t(1/2)) between the baseline and double-dose LPV/r time points."( Pharmacokinetics of lopinavir in HIV-infected adults receiving rifampin with adjusted doses of lopinavir-ritonavir tablets.
Decloedt, EH; Maartens, G; McIlleron, H; Merry, C; Orrell, C; Smith, P, 2011
)
" In part B, the safety, tolerability, and pharmacokinetic profile of AZD4877 at the MTD were evaluated."( A Phase I study to assess the safety, tolerability, and pharmacokinetics of AZD4877, an intravenous Eg5 inhibitor in patients with advanced solid tumors.
Burris, HA; Eckhardt, SG; Herbst, RS; Huszar, D; Hylander-Gans, L; Infante, JR; Kurzrock, R; Li, J; Osmukhina, A; Skolnik, JM; Spratlin, J; Wu, K, 2012
)
" The clinical pharmacokinetic and safety profile has enabled us to progress the compound to test its efficacy in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and a paper describing its efficacy has recently been published."( The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics.
Ballard, S; Barber, C; Barker, L; Beaumont, K; Bunnage, M; Cole, S; Corless, M; Denton, S; Ellis, D; Floc'h, M; Foster, L; Gosset, J; Holmwood, F; Lane, C; Leahy, D; Mathias, J; Maw, G; Million, W; Poinsard, C; Price, J; Rawson, DJ; Russel, R; Street, S; Watson, L, 2012
)
" The pharmacokinetic profile of 10 and 21 with adequate CNS penetration, required for in vivo Parkinson's disease models, are disclosed."( Isothiazole and isoxazole fused pyrimidones as PDE7 inhibitors: SAR and pharmacokinetic evaluation.
Bajpai, M; Banerjee, A; Gharat, LA; Gudi, GS; Gullapalli, S; Sangana, RR; Yadav, PS, 2012
)
" The mirodenafil base and hydrochloride salt forms showed similar pharmacokinetic profiles in terms of their maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC)."( Validated LC-MS/MS method for the determination of mirodenafil in rat plasma and its application to a comparative pharmacokinetic study of the free base and hydrochloride salt forms of mirodenafil.
Kim, TK; Park, JH; Yoo, HH, 2012
)
" The study was in three parts: dose escalation to define the maximum tolerated dose; identification of the recommended phase 2 dose; and assessment of pharmacodynamic changes."( Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial.
Becerra, C; Bendell, JC; Burris, HA; Cox, DS; DeMarini, DJ; Eckhardt, G; Falchook, GS; Fecher, LA; Flaherty, K; Gordon, MS; Hart, L; Infante, JR; Kurzrock, R; Le, NT; Messersmith, WA; Morris, SR; Nallapareddy, S; Peddareddigari, VG; Xu, Y, 2012
)
" The effective half-life of trametinib was about 4 days."( Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial.
Becerra, C; Bendell, JC; Burris, HA; Cox, DS; DeMarini, DJ; Eckhardt, G; Falchook, GS; Fecher, LA; Flaherty, K; Gordon, MS; Hart, L; Infante, JR; Kurzrock, R; Le, NT; Messersmith, WA; Morris, SR; Nallapareddy, S; Peddareddigari, VG; Xu, Y, 2012
)
" The measured individual plasma concentrations were used to calculate the pharmacokinetic parameters using noncompartmental methods."( Assessment of the influence of severe renal impairment on the pharmacokinetics of mirodenafil in Korean male volunteers.
Bae, KS; Chang, JW; Cho, SH; Choe, S; Ghim, JL; Jin, SJ; Jung, JA; Kim, MJ; Kim, SB; Kim, YH; Lee, B; Lee, SK; Lim, HS; Noh, YH; Park, JS; Yang, WS, 2012
)
" The method was successfully applied to a pharmacokinetic study after the intravenous administration of nifekalant hydrochloride to beagle dogs."( An HPLC method for the determination of nifekalant hydrochloride in canine plasma and its application to a pharmacokinetic study.
Jiang, XH; Liu, XM; Wang, L; Zhou, Y, 2013
)
" The design of this 2 treatment, 2 period crossover, incomplete wash-out study was influenced by the subject population, long half-life and PK variability; 24 subjects were randomized to a single, oral 2 mg trametinib dose administered in a fed/fasted state, followed by 7 days of serial PK sampling."( Evaluation of the effects of food on the single-dose pharmacokinetics of trametinib, a first-in-class MEK inhibitor, in patients with cancer.
Bauman, J; Cox, DS; Fang, L; LoRusso, P; Orford, K; Ouellet, D; Papadopoulos, K; Patnaik, A; Pendry, C; Tolcher, A, 2013
)
" The essential pharmacokinetic parameters of the intravenously injection of Nifekalant were found to be the following: t1/2=1."( The application of an LC-MS/MS method in a pharmacokinetic study for the determination of the concentration of nifekalant in human plasma.
An, Y; Shi, G; Sui, Y; Tang, Y; Yan, M; Zhang, M, 2013
)
" This manuscript outlines new developments in the SAR of a lead series of 1,2,3,4-tetrahydroisoquinoline derivatives with emphasis on strategies to improve pharmacokinetic properties and potency."( Optimization of potency and pharmacokinetic properties of tetrahydroisoquinoline transient receptor potential melastatin 8 (TRPM8) antagonists.
Bartberger, MD; Bo, Y; Clarine, J; Davis, CD; Gavva, NR; Gore, VK; Horne, DB; Kaller, MR; Lehto, SG; Ma, VV; Monenschein, H; Nguyen, TT; Nishimura, N; Norman, MH; Tamayo, NA; Tang, P; Wang, W; Youngblood, BD; Zhang, M, 2014
)
" and oral pharmacokinetic parameters, simultaneously."( Concomitant oral and intravenous pharmacokinetics of trametinib, a MEK inhibitor, in subjects with solid tumours.
Bauman, J; Fang, L; Henriquez, F; Ho, M; Leonowens, C; Morrison, RA; Orford, K; Ouellet, D; Pendry, C; Young, GC, 2014
)
" One of the compounds (1,3-bis(2-phenylethyl)pyrimidine-2,4,6(1H,3H,5H)-trione, (1) was previously found to have an excellent combination of potency efficacy, and some desirable pharmacokinetic properties."( Deuteration and fluorination of 1,3-bis(2-phenylethyl)pyrimidine-2,4,6(1H,3H,5H)-trione to improve its pharmacokinetic properties.
Benmohamed, R; Kirsch, DR; Morimoto, RI; Silverman, RB; Xia, G, 2014
)
"To evaluate the pharmacokinetic profiles of lopinavir (LPV) in Chinese HIV-infected patients."( [Pharmacokinetic profiles of lopinavir (LPV) in Chinese HIV-infected patients].
Du, X; Fu, Q; Li, T; Liu, Z; Zhang, X, 2015
)
"A total of 16 patients were enrolled in the LPV pharmacokinetic study."( [Pharmacokinetic profiles of lopinavir (LPV) in Chinese HIV-infected patients].
Du, X; Fu, Q; Li, T; Liu, Z; Zhang, X, 2015
)
"The non-compartment model pharmacokinetic (PK) parameters were as follows: the peak time of LPV (T(max)) (3."( [Pharmacokinetic profiles of lopinavir (LPV) in Chinese HIV-infected patients].
Du, X; Fu, Q; Li, T; Liu, Z; Zhang, X, 2015
)
"The pharmacokinetic profiles of LPV in Chinese HIV-1 infected patients demonstrate lower C(min) than those of reported studies, while other parameters are similar."( [Pharmacokinetic profiles of lopinavir (LPV) in Chinese HIV-infected patients].
Du, X; Fu, Q; Li, T; Liu, Z; Zhang, X, 2015
)
" Human pharmacokinetic predictions using single-species scaling of dog and/or monkey pharmacokinetics were consistent with the parameters observed in the first-in-human study, conducted in healthy volunteers at a dose range of 20-200 mg PF-06282999."( Pharmacokinetics and Disposition of the Thiouracil Derivative PF-06282999, an Orally Bioavailable, Irreversible Inactivator of Myeloperoxidase Enzyme, Across Animals and Humans.
Di, L; Dong, JQ; Feng, B; Kalgutkar, AS; Ryder, T; Sagawa, K; Terra, SG; Varma, MV; Wolford, A, 2016
)
"Trametinib concentrations obtained in three clinical studies were included in the population pharmacokinetic analysis."( Population pharmacokinetics and exposure-response of trametinib, a MEK inhibitor, in patients with BRAF V600 mutation-positive melanoma.
Chiu, J; Cox, D; Crist, W; DeMarini, DJ; Gardner, O; Kassir, N; Leonowens, C; Mouksassi, MS; Ouellet, D; Patel, K, 2016
)
" GSK2647544 was readily absorbed and its plasma concentration declined bi-exponentially with a terminal half-life ranging from 8 to 16 hours."( Evaluation of the safety, pharmacokinetics, pharmacodynamics, and drug-drug interaction potential of a selective Lp-PLA2 inhibitor (GSK2647544) in healthy volunteers
.
Fong, R; Gray, F; Guiney, W; Lockhart, A; Wu, K; Xu, J; Xu, Y; Yao, X, 2016
)
" Pharmacokinetic profiling of dabrafenib was undertaken, and its metabolites were similar pre- and post-dialysis and comparable to those in patients with normal renal function."( Pharmacokinetics of dabrafenib in a patient with metastatic melanoma undergoing haemodialysis.
Boddy, AV; Carlino, MS; Harris, D; Kefford, RF; Lee, V; Liu, X; Park, JJ, 2017
)
" This assay was successfully applied to pharmacokinetic and murine 4T1 breast tumor xenograft studies of AZD3965 in mice."( Development and validation of a liquid chromatography tandem mass spectrometry assay for AZD3965 in mouse plasma and tumor tissue: Application to pharmacokinetic and breast tumor xenograft studies.
Guan, X; Morris, ME; Ruszaj, D, 2018
)
" The objectives of this work were to develop a population pharmacokinetic (PopPK) model for AZD3241 and to investigate the correlation between AZD3241 exposure and myeloperoxidase inhibition."( Population Pharmacokinetic Modeling With Enterohepatic Circulation for AZD3241 in Healthy Subjects and Patients With Multiple System Atrophy.
Al-Huniti, N; Li, J; Li, Y; Mullen, JA; Savage, A; Taylor, W; Tong, X; Xu, H; Zhou, D, 2018
)
" Pharmacokinetic analysis may provide an explanation for the pyrexia."( Pharmacokinetic and cytokine profiles of melanoma patients with dabrafenib and trametinib-induced pyrexia.
Boddy, AV; Duong, JK; Gonzalez, M; Kim, HY; Lee, J; Lim, SY; Long, GV; Menzies, AM; Rizos, H, 2019
)
" Exposure to adavosertib, as determined by pharmacokinetic analysis, in Asian patients was higher than that previously seen in Western patients."( Safety, Pharmacokinetics, and Clinical Activity of Adavosertib in Combination with Chemotherapy in Asian Patients with Advanced Solid Tumors: Phase Ib Study.
Bang, YJ; de Souza, P; Kato, H; Kim, SW; Kumar, S; Lickliter, JD; Mugundu, GM; Naito, Y; Park, K, 2020
)
" Tegoprazan 50 mg or revaprazan 200 mg was administered orally, once daily for 7 days; 24-h intragastric pH monitoring and serum gastrin were measured for pharmacodynamic evaluation."( Pharmacodynamics of tegoprazan and revaprazan after single and multiple oral doses in healthy subjects.
Ban, MS; Jang, IJ; Ji, SC; Kim, B; Lee, S; Nam, JY; Oh, J; Song, GS; Sunwoo, J; Yu, KS, 2020
)
" Blood samples were collected at the designated time points for pharmacokinetic analysis."( A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TPN171H, a Novel Phosphodiesterase Type 5 Inhibitor, in Healthy Subjects.
Chen, Q; Jia, J; Jiang, H; Li, T; Liang, L; Pu, H; Qian, H; Shen, J; Song, R; Tian, G; Wang, Y; Wang, Z; Xin, L; Yu, C; Zhu, H; Zou, Y, 2021
)
" This study was designed to evaluate RP2D, maximum tolerated dose (MTD), and pharmacokinetic (PK) profile of trametinib in patients with advanced solid tumors who had various degrees of hepatic dysfunction (HD)."( Phase I pharmacokinetic study of single agent trametinib in patients with advanced cancer and hepatic dysfunction.
Bedard, PL; Chen, EX; Chen, HX; Hansen, AR; Hotte, SJ; Ivy, SP; Kelly, K; Lockhart, AC; Razak, AR; Renouf, DJ; Sahebjam, S; Singh, A; Siu, LL; Spreafico, A; Stayner, LA; Subbiah, V; Vaishampayan, UN; Voon, PJ; Wang, L, 2022
)

Compound-Compound Interactions

ExcerptReference
" The effectiveness of the histamine H2-receptor antagonist, SKF 93479, in preventing gizzard ulcerations when given in combination with cysteamine-HCl was also examined."( Gizzard ulceration in chicks fed cysteamine alone or in combination with a histamine H2-receptor antagonist.
Hedde, RD; Lindsey, TO; Zavy, MT, 1988
)
" However, treatment with NY 3170 in combination with cis-DDP induced increased cell inactivating effects equal to a doubling of either the concentration of cis-DDP or treatment time."( Synergistic cell inactivation by cis-dichlorodiammineplatinum in combination with 1-propargyl-5-chloropyrimidin-2-one.
Dornish, JM; Oftebro, R; Pettersen, EO, 1987
)
"Inactivating effects caused by vincristine alone or in combination with another mitotic inhibitor, 1-propargyl-5-chloropyrimidin-2-one, were studied as loss of colony-forming ability in exponentially growing or synchronized populations of the human cell line NHIK 3025."( Age-dependent cell inactivation by vincristine alone or in combination with 1-propargyl-5-chloropyrimidin-2-one.
Wibe, E, 1980
)
"0 microM) were marginal and are not likely to produce clinically significant drug-drug interactions."( Potent inhibition of the cytochrome P-450 3A-mediated human liver microsomal metabolism of a novel HIV protease inhibitor by ritonavir: A positive drug-drug interaction.
Dykstra, J; Granneman, GR; Hickman, D; Jayanti, VK; Kumar, GN; Roberts, EM; Surber, B; Thomas, S; Uchic, J; Yao, Y, 1999
)
"High-dose chemotherapy combined with autologous stem cell support has improved response rates in high-risk and metastatic breast cancer, but has failed to improve long-term survival."( Anti-tumor effect of Merocyanine 540-mediated photochemotherapy combined with Edelfosine: potential implications for the ex vivo purging of hematopoietic stem cell grafts from breast cancer patients.
Anderson, GS; Miyagi, K; Sampson, RW; Sieber, F, 2002
)
"The steady-state pharmacokinetics and pharmacodynamics of two oral doses of lopinavir-ritonavir (lopinavir/r; 400/100 and 533/133 mg) twice daily (BID) when dosed in combination with efavirenz, plus two nucleoside reverse transcriptase inhibitors, were assessed in a phase II, open-label, randomized, parallel arm study in 57 multiple protease inhibitor-experienced but non-nucleoside reverse transcriptase inhibitor-naive human immunodeficiency virus (HIV)-infected subjects."( Pharmacokinetic-pharmacodynamic analysis of lopinavir-ritonavir in combination with efavirenz and two nucleoside reverse transcriptase inhibitors in extensively pretreated human immunodeficiency virus-infected patients.
Bernstein, B; Bertz, R; Brun, S; Foit, C; Granneman, GR; Hsu, A; Isaacson, J; Kempf, DJ; King, M; Lam, W; Richards, B; Rode, R; Rynkiewicz, K; Sun, E, 2003
)
"The purpose of this study was to determine in a preclinical purging model, how effective crystal violet-mediated photodynamic therapy (CV-PDT) is against solid tumor and drug-resistant mutant tumor cells, and if certain limitations of CV-PDT can be overcome by using crystal violet (CV) in combination with the membrane-active photosensitizer, Merocyanine 540 (MC540)."( Crystal violet combined with Merocyanine 540 for the ex vivo purging of hematopoietic stem cell grafts.
Miyagi, K; Sampson, RW; Sieber, F; Sieber-Blum, M, 2003
)
" This study was carried out to examine the ability of exogenous zeaxanthin alone and in combination with vitamin E or C, to protect cultured human retinal pigment epithelium cells against oxidative stress."( Zeaxanthin in combination with ascorbic acid or alpha-tocopherol protects ARPE-19 cells against photosensitized peroxidation of lipids.
Rózanowska, M; Sarna, T; Wrona, M, 2004
)
"We describe a drug-drug interaction between coformulated lopinavir/ritonavir and itraconazole in a patient infected with human immunodeficiency virus type 1 who had disseminated histoplasmosis."( Drug-drug interaction between itraconazole and the antiretroviral drug lopinavir/ritonavir in an HIV-1-infected patient with disseminated histoplasmosis.
Beijnen, JH; Crommentuyn, KM; Huitema, AD; Mulder, JW; Schellens, JH; Sparidans, RW, 2004
)
" In the present study, two adjusted-dose regimens of lopinavir-ritonavir were tested in combination with rifampin."( Pharmacokinetics of adjusted-dose lopinavir-ritonavir combined with rifampin in healthy volunteers.
Bertz, R; Boeree, MJ; Burger, DM; Colbers, EP; Hekster, YA; Koopmans, PP; la Porte, CJ; Voncken, DS; Wikstrom, K, 2004
)
" The tissue distribution of radioactivity was examined in rats dosed with [14C]lopinavir in combination with ritonavir."( Metabolism and disposition of the HIV-1 protease inhibitor lopinavir (ABT-378) given in combination with ritonavir in rats, dogs, and humans.
Denissen, JF; Grabowski, BA; Jayanti, VK; Johnson, MK; Kempf, DJ; Kumar, GN; Lee, RD; Marsh, KC; Roberts, SA; Sham, HL; Sun, E; Thomas, S; Uchic, J, 2004
)
"To develop a population pharmacokinetic model for lopinavir in combination with ritonavir, in which the interaction between both drugs was characterized, and in which relationships between patient characteristics and pharmacokinetics were identified."( Population pharmacokinetics of lopinavir in combination with ritonavir in HIV-1-infected patients.
Beijnen, JH; Crommentuyn, KM; Huitema, AD; Kappelhoff, BS; Mairuhu, AT; Meenhorst, PL; Mulder, JW; van Gorp, EC, 2005
)
"Two phase I studies were conducted to assess the plasma pharmacokinetics of telbivudine and potential drug-drug interactions between telbivudine (200 or 600 mg/day) and lamivudine (100 mg/day) or adefovir dipivoxil (10 mg/day) in healthy subjects."( Pharmacokinetics of telbivudine in healthy subjects and absence of drug interaction with lamivudine or adefovir dipivoxil.
Brown, NA; Chao, GC; Fielman, BA; Lloyd, DM; Zhou, XJ, 2006
)
" Fosamprenavir-ritonavir has shown similar efficacy and safety to lopinavir-ritonavir when each is combined with two nucleoside reverse transcriptase inhibitors."( The KLEAN study of fosamprenavir-ritonavir versus lopinavir-ritonavir, each in combination with abacavir-lamivudine, for initial treatment of HIV infection over 48 weeks: a randomised non-inferiority trial.
DeJesus, E; Eron, J; Estrada, V; Gathe, J; Katlama, C; Lackey, P; Patel, L; Shaefer, M; Staszewski, S; Sutherland-Phillips, D; Vavro, C; Wannamaker, P; Yau, L; Yeni, P; Yeo, J; Young, B, 2006
)
"Fosamprenavir-ritonavir twice daily in treatment-naive patients provides similar antiviral efficacy, safety, tolerability, and emergence of resistance as lopinavir-ritonavir, each in combination with abacavir-lamivudine."( The KLEAN study of fosamprenavir-ritonavir versus lopinavir-ritonavir, each in combination with abacavir-lamivudine, for initial treatment of HIV infection over 48 weeks: a randomised non-inferiority trial.
DeJesus, E; Eron, J; Estrada, V; Gathe, J; Katlama, C; Lackey, P; Patel, L; Shaefer, M; Staszewski, S; Sutherland-Phillips, D; Vavro, C; Wannamaker, P; Yau, L; Yeni, P; Yeo, J; Young, B, 2006
)
" Together, these in vitro results indicate that combination with other antiretrovirals does not significantly increase the toxic potential of TFV in RPTECs."( In vitro cytotoxicity and mitochondrial toxicity of tenofovir alone and in combination with other antiretrovirals in human renal proximal tubule cells.
Alvarez, ML; Cihlar, T; Cordobilla, B; Domingo, JC; Domingo, P; Giralt, M; Guallar, J; López-Dupla, M; Sánchez de la Rosa, R; Saumoy, M; Torres, F; Vidal, F; Villarroya, F, 2006
)
"Our objective was to identify possible differences in protease inhibitor plasma concentrations between and within three protease inhibitor regimens (indinavir, saquinavir and lopinavir all in combination with low-dose ritonavir) and to relate these differences to safety and efficacy."( Pharmacokinetics of two randomized trials evaluating the safety and efficacy of indinavir, saquinavir and lopinavir in combination with low-dose ritonavir: the MaxCmin1 and 2 trials.
Cahn, P; Castagna, A; Clumeck, N; Dragsted, UB; Fox, Z; Gerstoft, J; Justesen, US; Losso, M; Lundgren, JD; Obel, N; Pedersen, C; Peters, B, 2007
)
"7-fold in combination with lopinavir/ritonavir."( Drug/Drug interaction between lopinavir/ritonavir and rosuvastatin in healthy volunteers.
Flynn, DM; Gerber, JG; Hoody, DW; Kiser, JJ; Predhomme, JA; Wolfe, P, 2008
)
"HIV-1-infected men enrolled in the Monark randomized trial were eligible for the present study after 48 weeks of a first-line lopinavir/ritonavir alone or in combination with zidovudine and lamivudine."( Absence of HIV-1 shedding in male genital tract after 1 year of first-line lopinavir/ritonavir alone or in combination with zidovudine/lamivudine.
Bresson, JL; Chaix, ML; Cohen-Codar, I; Delfraissy, JF; Galimand, J; Ghosn, J; Girard, PM; Peytavin, G; Raffi, F; Rouzioux, C, 2008
)
" Patients with HIV may also have simultaneous chronic medical conditions, resulting in the possibility of complex drug-drug interactions."( Possible antiretroviral therapy-warfarin drug interaction.
Fulco, PP; Higginson, RT; Zingone, MM, 2008
)
"In this open-label, international non-inferiority study, 883 antiretroviral-naive, HIV-1-infected patients were randomly assigned to receive atazanavir/ritonavir 300/100 mg once daily (n=440) or lopinavir/ritonavir 400/100 mg twice daily (n=443), in combination with fixed-dose tenofovir/emtricitabine 300/200 mg once daily."( Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study.
Andrade-Villanueva, J; Chetchotisakd, P; Corral, J; David, N; Echevarria, J; Mancini, M; McGrath, D; Molina, JM; Moyle, G; Percival, L; Thiry, A; Yang, R, 2008
)
"A total of 191 patients were randomized 2:2:2:1 to one of three APL dosing regimens or to lamivudine (3TC)/zidovudine (ZDV) twice daily (bid), each in combination with lopinavir/ritonavir (LPV/r) 400 mg/100 mg bid."( Antiviral activity and safety of aplaviroc, a CCR5 antagonist, in combination with lopinavir/ritonavir in HIV-infected, therapy-naïve patients: results of the EPIC study (CCR100136).
Adkison, KK; Berger, D; Bonny, T; Cimoch, P; Lamarca, A; Lazzarin, A; Madison, SJ; McCarty, D; Millard, J; Nichols, WG; Salvato, P; Smaill, FM; Teofilo, E; Yeni, P, 2009
)
"The KLEAN study extension assessed the long-term efficacy and safety of fosamprenavir-ritonavir (FPV/r) and lopinavir-ritonavir (LPV/r), both administered with abacavir/lamivudine (ABC/3TC) fixed dose combination, over 144 weeks."( Long-term efficacy and safety of fosamprenavir plus ritonavir versus lopinavir/ritonavir in combination with abacavir/lamivudine over 144 weeks.
Baril, JG; Duiculescu, D; Estrada, V; Lim, ML; Logue, K; Pharo, C; Plettenberg, A; Pulido, F; Schewe, K; Vavro, C; Yau, L,
)
"The findings of the KLEAN study extension (48 to 144 weeks) support durable viral suppression with both FPV/r and LPV/r treatment regimens when used in combination with ABC/3TC irrespective of viral load at baseline."( Long-term efficacy and safety of fosamprenavir plus ritonavir versus lopinavir/ritonavir in combination with abacavir/lamivudine over 144 weeks.
Baril, JG; Duiculescu, D; Estrada, V; Lim, ML; Logue, K; Pharo, C; Plettenberg, A; Pulido, F; Schewe, K; Vavro, C; Yau, L,
)
"Similar virological efficacy was observed for efavirenz and lopinavir/r, when administered with Kivexa in antiretroviral-naïve patients, while immunological improvement was slightly superior for efavirenz."( Similar antiviral efficacy and tolerability between efavirenz and lopinavir/ritonavir, administered with abacavir/lamivudine (Kivexa), in antiretroviral-naïve patients: a 48-week, multicentre, randomized study (Lake Study).
Bravo, I; Carosi, G; Clotet, B; del Arco, A; Echeverría, P; Gálvez, J; Gómez, JL; López, JC; López-Blazquez, R; Mariño, A; Moreno, A; Negredo, E; Ocampo, A; Pedrol, E; Pérez-Alvarez, N; Portilla, J; Prieto, A; Rubio, R; Viladés, C, 2010
)
"International, multicenter, open-label, 96-week noninferiority randomized trial of atazanavir/ritonavir 300/100 mg once daily vs lopinavir/ritonavir 400/100 mg twice daily, each in combination with fixed-dose tenofovir/emtricitabine 300/200 mg once daily, in antiretroviral-naive, HIV-1-infected patients."( Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 96-week efficacy and safety results of the CASTLE study.
Absalon, J; Andrade-Villanueva, J; Chetchotisakd, P; Corral, J; David, N; Echevarria, J; Lataillade, M; Mancini, M; McGrath, D; Molina, JM; Moyle, G; Percival, L; Wirtz, V; Yang, R, 2010
)
" We investigated the activity of clevudine (CLV) in combination with other nucleoside/nucleotide analogues to determine if these combinations were compatible in vitro."( Evaluation of the in vitro anti-HBV activity of clevudine in combination with other nucleoside/nucleotide inhibitors.
Bao, H; Furman, PA; Korba, B; Micolochick Steuer, HM; Murakami, E; Niu, C; Tolstykh, T, 2010
)
"Using the HepAD38 cell line, which expresses wild-type HBV, and a real-time PCR assay, we tested the anti-HBV activity of CLV in combination with entecavir, lamivudine, adefovir, tenofovir and telbivudine (TBV)."( Evaluation of the in vitro anti-HBV activity of clevudine in combination with other nucleoside/nucleotide inhibitors.
Bao, H; Furman, PA; Korba, B; Micolochick Steuer, HM; Murakami, E; Niu, C; Tolstykh, T, 2010
)
"When CLV was combined with entecavir, lamivudine, adefovir or tenofovir, a synergistic antiviral effect was observed; however, the combination of CLV and TBV gave an antagonistic antiviral response."( Evaluation of the in vitro anti-HBV activity of clevudine in combination with other nucleoside/nucleotide inhibitors.
Bao, H; Furman, PA; Korba, B; Micolochick Steuer, HM; Murakami, E; Niu, C; Tolstykh, T, 2010
)
"Increasing the ritonavir dose to achieve a lopinavir/ritonavir ratio of 1:1 when given in combination with rifampicin-based TB treatment did not completely compensate for the enhancement of lopinavir CL/F caused by rifampicin."( Population pharmacokinetics of lopinavir in combination with rifampicin-based antitubercular treatment in HIV-infected South African children.
Elsherbiny, D; Maartens, G; McIlleron, H; Ren, Y; Simonsson, US, 2010
)
"This phase 1b study determined the safety, tolerability, and recommended phase 2 dose (RP2D) and schedule of trametinib in combination with gemcitabine."( A phase 1b study of trametinib, an oral Mitogen-activated protein kinase kinase (MEK) inhibitor, in combination with gemcitabine in advanced solid tumours.
Bellew, KM; Bendell, JC; Burris, HA; Cox, DS; Durante, M; Infante, JR; Jones, SF; Le, NT; Papadopoulos, KP; Park, JJ; Patnaik, A; Rasco, D; Smith, L; Tolcher, AW, 2013
)
" During expansion, trametinib 2mg was combined with gemcitabine."( A phase 1b study of trametinib, an oral Mitogen-activated protein kinase kinase (MEK) inhibitor, in combination with gemcitabine in advanced solid tumours.
Bellew, KM; Bendell, JC; Burris, HA; Cox, DS; Durante, M; Infante, JR; Jones, SF; Le, NT; Papadopoulos, KP; Park, JJ; Patnaik, A; Rasco, D; Smith, L; Tolcher, AW, 2013
)
"Administration of trametinib at its full monotherapy dose of 2mg daily in combination with standard gemcitabine dosing (1000 mg/m(2) IV Days 1, 8, and 15 every 28 days) was feasible."( A phase 1b study of trametinib, an oral Mitogen-activated protein kinase kinase (MEK) inhibitor, in combination with gemcitabine in advanced solid tumours.
Bellew, KM; Bendell, JC; Burris, HA; Cox, DS; Durante, M; Infante, JR; Jones, SF; Le, NT; Papadopoulos, KP; Park, JJ; Patnaik, A; Rasco, D; Smith, L; Tolcher, AW, 2013
)
" Taken together, our findings offer preclinical proof of concept for dabrafenib as a specific and highly efficacious BRAF inhibitor and provide evidence for its potential clinical benefits when used in combination with a MEK inhibitor."( Dabrafenib; preclinical characterization, increased efficacy when combined with trametinib, while BRAF/MEK tool combination reduced skin lesions.
Arnone, MR; Bleam, MR; Erhardt, JA; Fedorowicz, KE; Hughes-Earle, A; Kane-Carson, LS; King, AJ; Laquerre, SG; Moss, KG; Qi, H; Rheault, TR; Sinnamon, RH; Smitheman, KN; Uehling, DE; Yang, J, 2013
)
" We treated six MM cell lines, representative of different histotypes (epithelioid, biphasic, and sarcomatoid), with cisplatin in combination with MK-1775, an inhibitor of the G 2/M checkpoint kinase WEE1."( Abrogating G₂/M checkpoint through WEE1 inhibition in combination with chemotherapy as a promising therapeutic approach for mesothelioma.
Alfano, L; Casini, N; Di Marzo, D; Forte, IM; Giordano, A; Giorgi, F; Indovina, P; Marcelli, E; Pentimalli, F, 2014
)
" Dabrafenib did not have an impact on T lymphocytes or moDCs, whereas trametinib alone or in combination with dabrafenib suppressed T-lymphocyte proliferation, cytokine production, and antigen-specific expansion."( MEK inhibition, alone or in combination with BRAF inhibition, affects multiple functions of isolated normal human lymphocytes and dendritic cells.
Andrews, M; Cebon, JS; Chen, W; Dimopoulos, N; Knights, A; Louahed, J; Pasam, A; Puaux, AL; Vella, LJ; Woods, K, 2014
)
"This phase Ib trial investigated the safety, tolerability, and recommended phase II dose and schedule of the MEK inhibitor trametinib in combination with the mammalian target of rapamycin (mTOR) inhibitor everolimus."( A phase IB trial of the oral MEK inhibitor trametinib (GSK1120212) in combination with everolimus in patients with advanced solid tumors.
Bellew, KM; Bendell, JC; Burris, HA; Cox, DS; Durante, M; Infante, JR; Jones, SF; Le, NT; Papadopoulos, KP; Park, J; Patnaik, A; Rasco, D; Tolcher, AW, 2015
)
" PK assessment did not suggest drug-drug interactions between these two agents."( A phase IB trial of the oral MEK inhibitor trametinib (GSK1120212) in combination with everolimus in patients with advanced solid tumors.
Bellew, KM; Bendell, JC; Burris, HA; Cox, DS; Durante, M; Infante, JR; Jones, SF; Le, NT; Papadopoulos, KP; Park, J; Patnaik, A; Rasco, D; Tolcher, AW, 2015
)
"This study was unable to identify a recommended phase II dose and schedule of trametinib in combination with everolimus that provided an acceptable tolerability and adequate drug exposure."( A phase IB trial of the oral MEK inhibitor trametinib (GSK1120212) in combination with everolimus in patients with advanced solid tumors.
Bellew, KM; Bendell, JC; Burris, HA; Cox, DS; Durante, M; Infante, JR; Jones, SF; Le, NT; Papadopoulos, KP; Park, J; Patnaik, A; Rasco, D; Tolcher, AW, 2015
)
"Trametinib can safely be given with weekly paclitaxel at the full monotherapy dose."( PACMEL: a phase 1 dose escalation trial of trametinib (GSK1120212) in combination with paclitaxel.
Ciria, C; Collins, L; Corrie, P; Coupe, N; Gore, M; Gupta, A; Hategan, M; Larkin, J; Love, S; Middleton, MR; Suter, S; Wise, A, 2015
)
"Wee1 regulates key DNA damage checkpoints, and in this study, the efficacy of the Wee1 inhibitor MK-1775 was evaluated in glioblastoma multiforme (GBM) xenograft models alone and in combination with radiation and/or temozolomide."( The Efficacy of the Wee1 Inhibitor MK-1775 Combined with Temozolomide Is Limited by Heterogeneous Distribution across the Blood-Brain Barrier in Glioblastoma.
Agar, NY; Bakken, KK; Calligaris, D; Carlson, BL; Decker, PA; Eckel-Passow, JE; Elmquist, WF; Evans, DL; Gupta, SK; Iyekegbe, DO; Lou, Z; Ma, B; Mueller, D; Pokorny, JL; Pucci, V; Sarkaria, JN; Schroeder, MA; Shumway, SD, 2015
)
"In vitro MK-1775 efficacy alone and in combination with temozolomide, and the impact on DNA damage, was analyzed by Western blotting and γH2AX foci formation."( The Efficacy of the Wee1 Inhibitor MK-1775 Combined with Temozolomide Is Limited by Heterogeneous Distribution across the Blood-Brain Barrier in Glioblastoma.
Agar, NY; Bakken, KK; Calligaris, D; Carlson, BL; Decker, PA; Eckel-Passow, JE; Elmquist, WF; Evans, DL; Gupta, SK; Iyekegbe, DO; Lou, Z; Ma, B; Mueller, D; Pokorny, JL; Pucci, V; Sarkaria, JN; Schroeder, MA; Shumway, SD, 2015
)
" However, there was no sensitizing effect of MK-1775 when combined with temozolomide in vitro."( The Efficacy of the Wee1 Inhibitor MK-1775 Combined with Temozolomide Is Limited by Heterogeneous Distribution across the Blood-Brain Barrier in Glioblastoma.
Agar, NY; Bakken, KK; Calligaris, D; Carlson, BL; Decker, PA; Eckel-Passow, JE; Elmquist, WF; Evans, DL; Gupta, SK; Iyekegbe, DO; Lou, Z; Ma, B; Mueller, D; Pokorny, JL; Pucci, V; Sarkaria, JN; Schroeder, MA; Shumway, SD, 2015
)
" In order to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of single-agent trametinib (part 1) and trametinib in combination with gemcitabine (part 2), we undertook the first clinical study of this combination in Japanese patients with cancer and herein report our results."( A phase I/Ib study of trametinib (GSK1120212) alone and in combination with gemcitabine in Japanese patients with advanced solid tumors.
Fujisaka, Y; Furuse, J; Kasuga, A; Kitamura, H; Kurata, T; Matsushita, H; Mukaiyama, A; Nagashima, F; Nakagawa, K; Naruge, D; Nishimura, Y; Nishina, S; Okamoto, W; Shimizu, T; Takasu, A, 2015
)
"0 mg once daily) in combination with gemcitabine (1000 mg/m(2))."( A phase I/Ib study of trametinib (GSK1120212) alone and in combination with gemcitabine in Japanese patients with advanced solid tumors.
Fujisaka, Y; Furuse, J; Kasuga, A; Kitamura, H; Kurata, T; Matsushita, H; Mukaiyama, A; Nagashima, F; Nakagawa, K; Naruge, D; Nishimura, Y; Nishina, S; Okamoto, W; Shimizu, T; Takasu, A, 2015
)
" We found that cetuximab, in combination with chemotherapy, fostered ICD in CRC cells, which we measured via the endoplasmic reticulum (ER) stress response and an increase in phagocytosis by dendritic cells."( The EGFR-specific antibody cetuximab combined with chemotherapy triggers immunogenic cell death.
Bardelli, A; Bonaldi, T; Cancelliere, C; Conte, A; Cuomo, A; Di Fiore, PP; Magni, E; Penna, G; Pozzi, C; Ravenda, PS; Rescigno, M; Sigismund, S; Silvola, A; Spadoni, I; Zampino, MG, 2016
)
"To evaluate in healthy volunteers the safety, pharmacokinetics (PK), pharmacodynamics (PD), and drug-drug interaction (DDI) potential of GSK2647544, (a selective lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor)."( Evaluation of the safety, pharmacokinetics, pharmacodynamics, and drug-drug interaction potential of a selective Lp-PLA2 inhibitor (GSK2647544) in healthy volunteers
.
Fong, R; Gray, F; Guiney, W; Lockhart, A; Wu, K; Xu, J; Xu, Y; Yao, X, 2016
)
" These data suggest that MBZ, a well-tolerated off-patent approved drug, should be considered as a therapeutic option in combination with trametinib, for patients with NRASQ61mut or other non-V600E BRAF mutant melanomas."( The repurposed anthelmintic mebendazole in combination with trametinib suppresses refractory NRASQ61K melanoma.
Abdussamad, M; Atkins, MB; Byers, SW; Calvert, V; Chen, YS; Dakshanamurthy, S; Fang, HB; Gaur, A; Petricoin, EF; Rosenthal, DS; Simbulan-Rosenthal, CM; Zapas, J; Zhou, H, 2017
)
" Targeting AKT in combination with WEE1 (mitotic inhibitor kinase) seems to have potential to make AKT-based therapeutics effective clinically."( Moving Synergistically Acting Drug Combinations to the Clinic by Comparing Sequential versus Simultaneous Drug Administrations.
Berg, A; Dinavahi, SS; Drabick, JJ; Gowda, R; Neves, RI; Noory, MA; Robertson, GP, 2018
)
" In the present study, we show that gemcitabine (GEM) in combination with TRA was more effective than TRA alone."( MEK inhibitor trametinib in combination with gemcitabine regresses a patient-derived orthotopic xenograft (PDOX) pancreatic cancer nude mouse model.
Bouvet, M; Clary, B; Delong, JC; Hoffman, RM; Hwang, HK; Igarashi, K; Kawaguchi, K; Kiyuna, T; Lwin, TM; Miyake, K; Miyake, M; Murakami, T; Singh, SR; Unno, M, 2018
)
"Based on the mechanisms by which Wee1 inhibitor and cisplatin played their own role, a promising strategy of Wee1 inhibitor combined with cisplatin was proposed, which was investigated in gastric cancer (GC)."( Wee1 Inhibitor AZD1775 Combined with Cisplatin Potentiates Anticancer Activity against Gastric Cancer by Increasing DNA Damage and Cell Apoptosis.
Chen, D; Dong, B; Gao, J; Li, Z; Lin, X; Shen, L; Zhang, C; Zhang, X, 2018
)
"In this study we evaluated the multitargeted Janus kinase/TANK-binding kinase 1 (TBK1) inhibitor momelotinib combined with the mitogen/extracellular signal-related kinase (MEK)1/MEK2 inhibitor trametinib in patients with platinum-treated, refractory, metastatic, KRAS-mutated NSCLC."( Phase 1B Study of Momelotinib Combined With Trametinib in Metastatic, Kirsten Rat Sarcoma Viral Oncogene Homolog-Mutated Non-Small-Cell Lung Cancer After Platinum-Based Chemotherapy Treatment Failure.
Barbie, DA; Humeniuk, R; Kawashima, J; Kelly, K; Koczywas, M; Kong, S; Spira, A, 2018
)
" In this study, we built on our preclinical studies to evaluate the safety and efficacy of AZD1775 in combination with gemcitabine and radiation in patients with newly diagnosed locally advanced pancreatic cancer."( Dose Escalation Trial of the Wee1 Inhibitor Adavosertib (AZD1775) in Combination With Gemcitabine and Radiation for Patients With Locally Advanced Pancreatic Cancer.
Al-Hawaray, M; Cho, CS; Cuneo, KC; Devasia, T; Lawrence, TS; Maybaum, J; Morgan, MA; Nathan, H; Parsels, JD; Parsels, LA; Sahai, V; Schipper, MJ; Zalupski, MM, 2019
)
"AZD1775 in combination with gemcitabine and radiation therapy was well tolerated at a dose that produced target engagement in a surrogate tissue."( Dose Escalation Trial of the Wee1 Inhibitor Adavosertib (AZD1775) in Combination With Gemcitabine and Radiation for Patients With Locally Advanced Pancreatic Cancer.
Al-Hawaray, M; Cho, CS; Cuneo, KC; Devasia, T; Lawrence, TS; Maybaum, J; Morgan, MA; Nathan, H; Parsels, JD; Parsels, LA; Sahai, V; Schipper, MJ; Zalupski, MM, 2019
)
"We sought to determine safety and efficacy of the AKT inhibitor, GSK2141795, combined with the MEK inhibitor, trametinib, in endometrial cancer."( Safety lead-in of the MEK inhibitor trametinib in combination with GSK2141795, an AKT inhibitor, in patients with recurrent endometrial cancer: An NRG Oncology/GOG study.
Aghajanian, C; Birrer, MJ; Coleman, RL; Fracasso, PM; Ju, Z; Lee, S; Martin, LP; Mathews, CA; Mills, GB; Modesitt, SC; Moore, KN; Schilder, RJ; Sill, MW; Waggoner, S; Westin, SN, 2019
)
"This open-label Phase Ib study (NCT02341456) investigated the safety, pharmacokinetics, and clinical activity of adavosertib in combination with carboplatin alone or paclitaxel plus carboplatin in Asian patients with advanced solid tumors and defined the recommended Phase II dose."( Safety, Pharmacokinetics, and Clinical Activity of Adavosertib in Combination with Chemotherapy in Asian Patients with Advanced Solid Tumors: Phase Ib Study.
Bang, YJ; de Souza, P; Kato, H; Kim, SW; Kumar, S; Lickliter, JD; Mugundu, GM; Naito, Y; Park, K, 2020
)
" Two patients receiving adavosertib 225 mg bid in combination with paclitaxel plus carboplatin experienced dose-limiting toxicities (grade 4 sepsis; grade 5 acute respiratory distress syndrome); this regimen was not considered tolerable."( Safety, Pharmacokinetics, and Clinical Activity of Adavosertib in Combination with Chemotherapy in Asian Patients with Advanced Solid Tumors: Phase Ib Study.
Bang, YJ; de Souza, P; Kato, H; Kim, SW; Kumar, S; Lickliter, JD; Mugundu, GM; Naito, Y; Park, K, 2020
)
"5 days was chosen as the recommended Phase II dose in combination with paclitaxel and carboplatin in Asian patients."( Safety, Pharmacokinetics, and Clinical Activity of Adavosertib in Combination with Chemotherapy in Asian Patients with Advanced Solid Tumors: Phase Ib Study.
Bang, YJ; de Souza, P; Kato, H; Kim, SW; Kumar, S; Lickliter, JD; Mugundu, GM; Naito, Y; Park, K, 2020
)
"Continuous and intermittent dosing of trametinib in combination with uprosertib was not tolerated, and minimal clinical activity was observed in all schedules tested."( Phase I dose-escalation trial of the oral AKT inhibitor uprosertib in combination with the oral MEK1/MEK2 inhibitor trametinib in patients with solid tumors.
Becerra, C; D'Amelio, AM; Ellis, C; Gauvin, J; Gonzalez, R; Heist, RS; Ibrahim, N; Kalyana-Sundaram, S; Kleha, JF; Kurzrock, R; Leonowens, C; Means-Powell, J; Tan, AR; Tolcher, AW; Valero, V; Wang, C; Werner, TL; Yan, L, 2020
)
"Among patients with mTNBC treated with 0-1 prior lines, adavosertib combined with cisplatin missed the prespecified ORR cutoff of >30%."( Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer.
Anderson, L; Conway, J; D'Andrea, A; Davis, J; Godin, RE; Guerriero, JL; He, MX; Keenan, TE; Kochupurakkal, B; Li, T; Mittendorf, EA; Overmoyer, B; Pastorello, R; Shannon, E; Shapiro, GI; Sorger, PK; Tahara, RK; Tayob, N; Tolaney, SM; Vallius, T; Van Allen, EM; Winer, EP, 2021
)
" This phase 1, open-label, dose-escalation and -expansion study (NCT02027961) investigated safety, tolerability and preliminary efficacy of durvalumab (anti-PD-L1) combined with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) for patients with BRAF-mutated melanoma (cohort A, n = 26), or durvalumab and trametinib given concomitantly (cohort B, n = 20) or sequentially (cohort C, n = 22) for patients with BRAF-wild type melanoma."( PD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma.
Algazi, A; Ascierto, PA; Butler, MO; Campbell, KM; Chandra, S; Delafont, B; Gordon, M; Hernandez-Aya, L; Lawrence, D; Lutzky, J; Marshall, S; Miller, WH; Mueller, N; Ribas, A; Robert, C, 2020
)
" In vitro and in vivo studies revealed significant efficacy of MK-1775 (Wee1 inhibitor) in combination with avapritinib in KIT mutant and PDGFRA mutant GIST cell lines as well as notable efficacy of MK-1775 as a monotherapy in the engineered PDGFRA mutant line."( Identification of Wee1 as a target in combination with avapritinib for gastrointestinal stromal tumor treatment.
Belinsky, MG; D'Souza, J; DeMatteo, R; Devarajan, K; Duncan, JS; Einarson, MB; Heinrich, MC; Johnson, KJ; Klug, L; Kozinova, M; Litwin, S; Rink, L; Sharipova, D; von Mehren, M; Ye, S; Zhou, Y, 2021
)
" We evaluated the anticancer potential of metformin in combination with trametinib plus paclitaxel, against four melanoma cell lines."( Effect of Metformin in Combination With Trametinib and Paclitaxel on Cell Survival and Metastasis in Melanoma Cells.
Lee, Y; Park, D, 2021
)
" The combination with anti-PD-1 results in optimal treatment efficacy for iCCA."( Anti-PD-1 in Combination With Trametinib Suppresses Tumor Growth and Improves Survival of Intrahepatic Cholangiocarcinoma in Mice.
Diggs, LP; Green, BL; Greten, TF; Heinrich, B; Ma, C; McCallen, JD; McVey, JC; Ruf, B; Tandon, M; Wabitsch, S; Zhang, Q, 2021
)
" In this report, we describe the safe and effective use of trametinib combined with dasatinib in a patient with acute lymphoblastic leukemia (ALL)."( Successful use of trametinib and dasatinib combined with chemotherapy in the treatment of Ph-positive B-cell acute lymphoblastic leukemia: A case report.
Hu, BF; Shen, SH; Wang, GL; Wang, J, 2021
)
"The patient was treated with dasatinib combined with an intermediate risk-oriented chemotherapy."( Successful use of trametinib and dasatinib combined with chemotherapy in the treatment of Ph-positive B-cell acute lymphoblastic leukemia: A case report.
Hu, BF; Shen, SH; Wang, GL; Wang, J, 2021
)
" The authors conducted a phase 1b trial to evaluate the safety of adavosertib in combination with definitive chemoradiotherapy for patients with newly diagnosed, intermediate-risk/high-risk, locally advanced head and neck squamous cell carcinoma (HNSCC)."( Phase 1 trial of adavosertib (AZD1775) in combination with concurrent radiation and cisplatin for intermediate-risk and high-risk head and neck squamous cell carcinoma.
Chera, BS; Douglas, KE; Goldin, D; Green, RL; Grilley Olson, JE; Gupta, GP; Moore, DT; Patel, SA; Shen, CJ; Sheth, SH; Weiss, JM, 2021
)
" AMG 232 PK exposures were not altered when AMG 232 was combined with T±D."( Targeting wild-type TP53 using AMG 232 in combination with MAPK inhibition in Metastatic Melanoma; a phase 1 study.
Flaherty, KT; Henary, HA; Johnson, DB; Lewis, KD; Long, GV; Moschos, SJ; Puzanov, I; Sandhu, S; Sullivan, RJ; Upreti, VV; Wong, H, 2022
)
"We conducted a phase I study to evaluate the maximum tolerated dose (MTD), safety, and efficacy of trametinib in combination with TAS-102 in patients with chemotherapy-refractory KRAS-mutant, wild-type PIK3CA/PTEN metastatic colorectal cancer (mCRC)."( A Phase I Clinical Trial of Trametinib in Combination with TAS-102 in Patients with Chemotherapy-Resistant RAS-Mutated (PIK3CA/PTEN-Wild Type) Metastatic Colorectal Cancer.
Chuang, J; Fakih, M; Gong, J; Li, SM; Wang, C, 2022
)
"Trametinib in combination with TAS-102 demonstrated a manageable safety profile."( A Phase I Clinical Trial of Trametinib in Combination with TAS-102 in Patients with Chemotherapy-Resistant RAS-Mutated (PIK3CA/PTEN-Wild Type) Metastatic Colorectal Cancer.
Chuang, J; Fakih, M; Gong, J; Li, SM; Wang, C, 2022
)

Bioavailability

ExcerptReference
"This study in the rat established the effects that a broad-spectrum and poorly absorbed antibiotic, neomycin sulfate, had on the in vitro and in vivo hydrolysis of vicine and convicine by the intestinal microflora, and on vicine- and convicine-induced depletion of blood glutathione and the resulting toxicity."( Effect of neomycin on the hydrolysis and toxicity of vicine and convicine in rats.
Arbid, MS; Frohlich, AA; Madhyastha, MS; Marquardt, RR, 1993
)
" The results of pharmacokinetic studies suggest that the compound LM-1554 is poorly absorbed from the gastrointestinal tract after the oral administration in dogs and rabbits."( Mechanism of the antihyperlipaemic activity and pharmacokinetics of 2-chloromethyl-5,6,7,8-tetrahydrobenzo(b)thieno[2,3-d]pyrimidin-4(3H)-o ne.
Gandhi, TR; Goyal, RK; Jain, KS; Rathod, IS; Shishoo, CJ, 1997
)
"8 hr and a bioavailability of 30 to 50% in dogs."( Actions of A-131701, a novel, selective antagonist for alpha-1A compared with alpha-1B adrenoceptors on intraurethral and blood pressure responses in conscious dogs and a pharmacodynamic assessment of in vivo prostatic selectivity.
Brune, ME; Crowell, D; Hancock, AA; Ireland, LM; Katwala, S; Kerwin, JF; Marsh, KC; Meyer, MD; Milicic, I; Witte, DG, 1998
)
" In rat oral bioavailability studies, compound 63 plasma concentrations declined in a biexponential manner, and systemic plasma clearance was high relative to liver blood flow."( 2-Substituted aminopyrido[2,3-d]pyrimidin-7(8H)-ones. structure-activity relationships against selected tyrosine kinases and in vitro and in vivo anticancer activity.
Amar, AM; Boschelli, DH; Bradford, LA; Dahring, TK; Doherty, AM; Driscoll, DL; Dykes, DJ; Elliott, WL; Hallak, H; Hamby, JM; Hartl, BG; Klohs, WD; Klutchko, SR; Kraker, AJ; Lu, GH; Major, TC; Nelson, JM; Panek, RL; Roberts, BJ; Shen, C; Showalter, HD; Steinkampf, RW; Stoner, CL; Vincent, PW; Wu, Z, 1998
)
" The reason for the low extent of bioavailability (F) of YH1885 after oral administration of the drug to rats and the absorption of the drug from various rat gastrointestinal (GI) segments were also investigated."( Pharmacokinetics of a new reversible proton pump inhibitor, YH1885, after intravenous and oral administrations to rats and dogs: hepatic first-pass effect in rats.
Han, KS; Kim, YG; Lee, JW; Lee, MG; Yoo, JK, 1998
)
" Several of these compounds were examined for oral bioavailability in the rat or the dog at 10 mg/kg."( Stereospecific synthesis, structure-activity relationship, and oral bioavailability of tetrahydropyrimidin-2-one HIV protease inhibitors.
De Lucca, GV; De Lucca, I; Liang, J, 1999
)
" Bioavailability was attenuated by pre-systemic hepatic metabolism in all species."( Pharmacokinetics and metabolism of sildenafil in mouse, rat, rabbit, dog and man.
Ackland, MJ; James, GC; Muirhead, GJ; Rance, DJ; Walker, DK; Wastall, P; Wright, PA, 1999
)
" Oral administration of compounds 14a and 15a also produced a lasting antagonism to the hypomotility induced by CCK-8 in mice, suggesting a good bioavailability and metabolic stability."( 5-(Tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based potent and selective CCK(1) receptor antagonists: structural modifications at the tryptophan domain.
Ballaz, S; Bartolomé-Nebreda, JM; Cenarruzabeitia, E; Del Río, J; García-López, MT; Gómez-Monterrey, I; González-Muñiz, R; Herranz, R; LaTorre, M; Martín-Martínez, M, 1999
)
" While many of the compounds tested displayed poor pharmacokinetics, compound 48 was found to have adequate bioavailability (>20%) and half-life (>6 h) in both rats and dogs."( In vitro and in vivo evaluation of dihydropyrimidinone C-5 amides as potent and selective alpha(1A) receptor antagonists for the treatment of benign prostatic hyperplasia.
Barrish, A; Barrow, JC; Broten, TP; Chang, RS; Ellis, JD; Forray, C; Freidinger, RM; Gilbert, KF; Glass, KL; Homnick, CF; Kassahun, K; Kling, P; Leppert, P; Nagarathnam, D; Nantermet, PG; O'Malley, SS; Olah, TV; Ransom, RW; Reiss, D; Rittle, KE; Schorn, TW; Selnick, HG; Steele, TG, 2000
)
"3 microM), appears to contribute to the dose-dependent bioavailability of the drug."( The transport of a reversible proton pump antagonist, 5, 6-dimethyl-2-(4-Fluorophenylamino)-4-(1-methyl-1,2,3, 4-tetrahydroisoquinoline-2-yl) pyrimidine hydrochloride (YH1885), across caco-2 cell monolayers.
Chung, SJ; Kim, DC; Kim, HS; Lee, JW; Li, H; Shim, CK, 2001
)
" Pharmacokinetic studies in rats and dogs indicated that 2u was absorbed rapidly after oral administration and had satisfactory bioavailability in these experimental animal species (rat, 17%; dog, 32%)."( Synthesis, structure-activity relationships, and pharmacokinetic profiles of nonpeptidic difluoromethylene ketones as novel inhibitors of human chymase.
Akahoshi, F; Ashimori, A; Eda, M; Fukaya, C; Imada, T; Kuwahara, S; Mitsutomi, N; Miyazaki, M; Nakajima, M; Nakamura, N; Ohtsuka, T; Sakashita, H; Yoshimura, T, 2001
)
" BCX-1777 has excellent oral bioavailability (63%) in mice."( Purine nucleoside phosphorylase inhibitor BCX-1777 (Immucillin-H)--a novel potent and orally active immunosuppressive agent.
Ananth, SL; Bantia, S; Horn, LL; Hutchison, TL; Kilpatrick, JM; Miller, PJ; Montgomery, JA; Morris, PE; Parker, CD; Sandhu, JS, 2001
)
" Food significantly increased the bioavailability of fiduxosin."( Effect of food on the pharmacokinetics of fiduxosin in healthy male subjects.
Dutta, S; Granneman, GR; Verlinden, M; Zhang, Y,
)
"ONO-6818 (CP-955) is the lead compound in a series of orally bioavailable neutrophil elastase inhibitors licensed from Cortech and under investigation by Ono for the potential treatment of inflammatory conditions, such as rheumatoid arthritis, inflammatory bowel disease and chronic obstructive pulmonary disease (COPD) [174095]."( ONO-6818 Cortech/Ono.
Trifilieff, A, 2002
)
" The results demonstrated that the thienopyrimidine-2,4-dione core is an excellent surrogate for the thienopyridin-4-one and that thienopyrimidine-2,4-diones and thienopyridin-4-ones constitute a new class of potent and orally bioavailable LHRH receptor antagonists."( Discovery of a thieno[2,3-d]pyrimidine-2,4-dione bearing a p-methoxyureidophenyl moiety at the 6-position: a highly potent and orally bioavailable non-peptide antagonist for the human luteinizing hormone-releasing hormone receptor.
Cho, N; Endo, S; Fujino, M; Furuya, S; Harada, M; Nara, Y; Sasaki, S; Suzuki, N, 2003
)
" The model parameters volume of distribution and absorption rate constant were 61."( Population pharmacokinetics of lopinavir in combination with ritonavir in HIV-1-infected patients.
Beijnen, JH; Crommentuyn, KM; Huitema, AD; Kappelhoff, BS; Mairuhu, AT; Meenhorst, PL; Mulder, JW; van Gorp, EC, 2005
)
"9 L), absorption rate constant (0."( No significant influence of saquinavir hard-gel capsule administration on pharmacokinetics of lopinavir in combination with ritonavir: a population approach.
Allavena, C; Dailly, E; Gagnieu, MC; Jolliet, P; Raffi, F, 2005
)
" It has been shown that elements are poorly absorbed in their inorganic forms and required high doses which have been associated with undesirable side effects."( Syntheses of vanadyl and zinc(II) complexes of 1-hydroxy-4,5,6-substituted 2(1H)-pyrimidinones and their insulin-mimetic activities.
Adachi, Y; Katoh, A; Saito, R; Sakurai, H; Wakasugi, K; Yamaguchi, M; Yoshikawa, Y, 2006
)
" Many of these compounds are potent, selective, and orally bioavailable inhibitors of coagulation factor Xa."( Preparation of 1-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones as potent, selective and bioavailable inhibitors of coagulation factor Xa.
Bai, SA; Buriak, J; Cacciola, J; Fevig, JM; Knabb, RM; Lam, PY; Luettgen, JM; Rossi, KA; Wexler, RR; Wong, PC, 2006
)
" The in vivo oral and iv pharmacokinetic profiles of example compounds confirmed the high oral bioavailability predicted from these in vitro screens."( A novel series of potent and selective PDE5 inhibitors with potential for high and dose-independent oral bioavailability.
Allerton, CM; Barber, CG; Beaumont, KC; Brown, DG; Cole, SM; Ellis, D; Lane, CA; Maw, GN; Mount, NM; Rawson, DJ; Robinson, CM; Street, SD; Summerhill, NW, 2006
)
" The fexofenadine AUC(infinity) was increased by lopinavir/ritonavir, likely due to increased bioavailability secondary to P-glycoprotein inhibition."( Time-dependent interaction between lopinavir/ritonavir and fexofenadine.
Bourbeau, M; Cameron, DW; Campbell, P; Chauhan, BM; Foster, BC; Seguin, I; van Heeswijk, RP, 2006
)
" Despite high molecular weights, clogPs, and polar surface areas, the compounds are generally well absorbed and have excellent pharmacokinetic (PK) properties when dosed as sodium salts."( Potent, selective pyrimidinetrione-based inhibitors of MMP-13.
Antipas, AS; Berliner, MA; Datta, K; Downs, JT; Eskra, JD; Forman, MD; Freeman-Cook, KD; Greer, EM; Guzman, R; Hardink, JR; Janat, F; Jones, CS; Keene, NF; Laird, ER; Liras, JL; Lopresti-Morrow, LL; Martinelli, GJ; Mitchell, PG; Pandit, J; Reiter, LA; Robertson, D; Sperger, D; Vaughn-Bowser, ML; Waller, DM; Yocum, SA, 2006
)
"Lopinavir, an HIV protease inhibitor, is coformulated with ritonavir to enhance the bioavailability and pharmacokinetics of lopinavir."( The tablet formulation of lopinavir/ritonavir provides similar bioavailability to the soft-gelatin capsule formulation with less pharmacokinetic variability and diminished food effect.
Awni, W; Breitenbach, J; Brun, SC; Chiu, YL; Doan, T; Hanna, GJ; Heuser, RS; Klein, CE; Morris, JB; Zhu, T, 2007
)
" In conclusion, this study presents direct evidence that LVR is effluxed by both P-gp and MRP2 which may contribute to its poor oral bioavailability and limited penetration into the CNS."( Both P-gp and MRP2 mediate transport of Lopinavir, a protease inhibitor.
Agarwal, S; Mitra, AK; Pal, D, 2007
)
"SK-3530 was relatively well absorbed in the gastrointestinal tract and showed linear pharmacokinetics over the investigated dose range."( Pharmacokinetics and tissue distribution of a novel PDE5 inhibitor, SK-3530, in rats.
Im, GJ; Kim, DH; Kim, NS; Yoo, HH, 2007
)
"This investigation was carried out to evaluate the bioavailability of a new single fixed-dose combination formulation of lopinavir and ritonavir, relative to reference product, Kaletra (133."( A bioequivalence study comparing two formulations of lopinavir/ritonavir capsules.
Gurule, S; Khuroo, AH; Lao, VK; Mishra, S; Monif, T; Raghuvanshi, R; Thudi, NR; Tippabhotla, SK, 2008
)
" The results indicated that lopinavir bioavailability was not affected by the coadministration of omeprazole or ranitidine."( Effects of acid-reducing agents on the pharmacokinetics of lopinavir/ritonavir and ritonavir-boosted atazanavir.
Beck, K; Cai, Y; Causemaker, SJ; Chiu, YL; Doan, T; Esslinger, HU; Hanna, GJ; King, KR; Klein, CE; Podsadecki, TJ, 2008
)
"(R)-N-{1-[3-(4-Ethoxy-phenyl)-4-oxo-3,4-dihydro-pyrido[2,3-d]-pyrimidin-2-yl]-ethyl}-N-pyridin-3-yl-methyl-2-(4-trifluoromethoxyphenyl)-acetamide (AMG 487) is a potent and selective orally bioavailable chemokine (C-X-C motif) receptor 3 (CXCR3) antagonist that displays dose- and time-dependent pharmacokinetics in human subjects after multiple oral dosing."( An inhibitory metabolite leads to dose- and time-dependent pharmacokinetics of (R)-N-{1-[3-(4-ethoxy-phenyl)-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-yl]-ethyl}-N-pyridin-3-yl-methyl-2-(4-trifluoromethoxy-phenyl)-acetamide (AMG 487) in human subjects af
Berry, K; Cho, R; Floren, LC; Johnson, MG; Kersey, K; Ma, J; Marcus, AP; Medina, JC; Pearson, PG; Tonn, GR; Van Lengerich, B; Wang, X; Wong, BK; Wong, SC; Wong, SG, 2009
)
"In this study, we explored the bioavailability in dogs and chemical potency of generic ritonavir and lopinavir/ritonavir tablet products manufactured by various pharmaceutical companies."( Bioavailability of generic ritonavir and lopinavir/ritonavir tablet products in a dog model.
Garren, KW; Marsh, K; Morris, JB; Rahim, S, 2010
)
" Selected compounds were further evaluated for their oral anti-histaminic activity in mice and bioavailability in rats."( Synthesis and structure-activity relationships of phenothiazine carboxylic acids having pyrimidine-dione as novel histamine H(1) antagonists.
Isobe, Y; Kubota, K; Kurebayashi, H; Miyachi, H; Onishi, M; Tobe, M, 2009
)
" This compound has 90% oral bioavailability (rat) and excellent plasma exposure (dAUC 935 ng h/mL)."( Orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors.
Boze, MA; Brunn, SA; Chisholm, JW; Chu, N; Cole, AG; Glushkov, AI; Hao, J; Henderson, I; Koltun, DO; Leung, K; Mayboroda, EI; Mollova, N; Parkhill, EQ; Vasilevich, NI; Zablocki, J; Zautke, NA; Zilbershtein, TM, 2009
)
" A final model was built with identified covariates, including creatinine clearance on plasma clearance, dose and race on bioavailability fraction, and body weight on central volume of distribution."( Population pharmacokinetics of telbivudine and determination of dose adjustment for patients with renal impairment.
Farrell, C; Ke, J; Mayers, DL; Pentikis, HS; Sallas, WM; Zhou, XJ, 2009
)
" The ritonavir dose-dependence of boosting effects did not correlate with their bioavailability or their effects on ritonavir plasma levels."( How much ritonavir is needed to boost protease inhibitors? Systematic review of 17 dose-ranging pharmacokinetic trials.
Boffito, M; Hill, A; Sawyer, W; van der Lugt, J, 2009
)
" The pharmacokinetics of 14j was studied in CD-1 mice and shown to exhibit bioavailability of 76% after oral dosing."( Discovery of 3H-benzo[4,5]thieno[3,2-d]pyrimidin-4-ones as potent, highly selective, and orally bioavailable inhibitors of the human protooncogene proviral insertion site in moloney murine leukemia virus (PIM) kinases.
Bouska, JJ; Giranda, VS; Guan, R; Han, EK; Hasvold, LA; Johnson, EF; Leverson, JD; Lin, NH; Luo, Y; Penning, TD; Rosenberg, SH; Soni, N; Sowin, TJ; Stamper, G; Stewart, KD; Stoll, VS; Tao, ZF, 2009
)
" Meltrex) have proven to be a promising formulation tool for poorly water-soluble and poorly bioavailable drugs."( In situ formation of nanoparticles upon dispersion of melt extrudate formulations in aqueous medium assessed by asymmetrical flow field-flow fractionation.
Brandl, M; Fricker, G; Hölig, P; Hupfeld, S; Kanzer, J; Mägerlein, M; Tho, I; Vasskog, T, 2010
)
"Telbivudine is an orally bioavailable L-nucleoside with potent and specific anti-hepatitis B virus activity."( Telbivudine preserves T-helper 1 cytokine production and downregulates programmed death ligand 1 in a mouse model of viral hepatitis.
Chen, T; Guo, W; Lu, YL; Luo, XP; Ning, Q; Wang, HW; Wang, XJ; Wu, ZG; Yan, WM; Yang, XJ; Zou, Y, 2010
)
" We also evaluated whether ritonavir increases lopinavir oral bioavailability by inhibition of CYP3A, ABCB1 and/or ABCC2."( Effects of cytochrome P450 3A (CYP3A) and the drug transporters P-glycoprotein (MDR1/ABCB1) and MRP2 (ABCC2) on the pharmacokinetics of lopinavir.
Beijnen, JH; Huitema, AD; Rooswinkel, RW; Schinkel, AH; ter Heine, R; van der Kruijssen, CM; van Waterschoot, RA; Wagenaar, E, 2010
)
" Both intestinal and hepatic CYP3A activity contributed importantly to low oral bioavailability of lopinavir."( Effects of cytochrome P450 3A (CYP3A) and the drug transporters P-glycoprotein (MDR1/ABCB1) and MRP2 (ABCC2) on the pharmacokinetics of lopinavir.
Beijnen, JH; Huitema, AD; Rooswinkel, RW; Schinkel, AH; ter Heine, R; van der Kruijssen, CM; van Waterschoot, RA; Wagenaar, E, 2010
)
" The percentage bioavailability was significantly enhanced."( Lopinavir loaded solid lipid nanoparticles (SLN) for intestinal lymphatic targeting.
Aji Alex, MR; Chacko, AJ; Jose, S; Souto, EB, 2011
)
" One of these compounds was found to have good oral bioavailability and PK/PD profile in ZF-rat."( Discovery of new chemotype dipeptidyl peptidase IV inhibitors having (R)-3-amino-3-methyl piperidine as a pharmacophore.
Horiguchi, M; Kimura, H; Masui, Y; Nakagawa, T; Nakahira, H; Nishio, Y; Ono, M; Sakai, M; Sugaru, E; Tosaki, S, 2010
)
" Since poor bioavailability and limited in vivo half-life are common features of hydrophobic PI3K inhibitors, our results open the way to similar formulation of other PI3K blockers and to new strategies in cancer treatment."( Sustained release of PI3K inhibitor from PHA nanoparticles and in vitro growth inhibition of cancer cell lines.
Chen, GQ; Ciraolo, E; Hirsch, E; Lu, XY; Stefenia, R; Zhang, Y, 2011
)
" However, due to poor water solubility, oral bioavailability of the drug was relatively low."( Preparation and in vitro/in vivo evaluation of revaprazan hydrochloride nanosuspension.
Chen, Y; Fang, L; Li, W; Mu, L; Tian, Y; Xu, X; Yang, Y; Zhang, Y, 2011
)
"0%), and the apparent volume of distribution and absorption rate constant were 55."( Sequential population pharmacokinetic modeling of lopinavir and ritonavir in healthy volunteers and assessment of different dosing strategies.
Aarons, L; Back, D; Boffito, M; Davies, G; Dickinson, L; Else, L; Khoo, S; Moyle, G; Pozniak, A; von Hentig, N, 2011
)
" Systemic exposure was prolonged with the modified release formulation, but bioavailability was reduced in comparison with that of the immediate release formulation."( Application of physiologically based pharmacokinetic modeling to understanding the clinical pharmacokinetics of UK-369,003.
Davis, J; Jones, HM; Watson, KJ, 2011
)
" Compound 10 exhibited a significantly enhanced dissolution rate compared to 1, translating to a high oral bioavailability (>90%) in rat."( Substituted N-aryl-6-pyrimidinones: a new class of potent, selective, and orally active p38 MAP kinase inhibitors.
Anderson, GD; Devadas, B; Devraj, RV; Madsen, HM; Marrufo, LD; Messing, DM; Monahan, JB; Morgan, HM; Selness, SR; Shieh, H; Webb, EG; Xing, L; Yang, JZ; Zhang, J, 2011
)
"The objective of this paper was to identify oral bioavailability enhancing approaches for a poorly water-soluble research compound during drug discovery stages using minimal amounts of material."( Selection of oral bioavailability enhancing formulations during drug discovery.
Dannenfelser, RM; Garad, S; Jain, A; Panicucci, R; Papoutsakis, D; Zheng, W, 2012
)
"This paper describes our recent efforts to design and synthesise potent and selective PDE5 inhibitors and the use of in vitro predictors of clearance, absorption and permeability to maximise the potential for dose-proportional pharmacokinetics and good oral bioavailability in man."( The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics.
Ballard, S; Barber, C; Barker, L; Beaumont, K; Bunnage, M; Cole, S; Corless, M; Denton, S; Ellis, D; Floc'h, M; Foster, L; Gosset, J; Holmwood, F; Lane, C; Leahy, D; Mathias, J; Maw, G; Million, W; Poinsard, C; Price, J; Rawson, DJ; Russel, R; Street, S; Watson, L, 2012
)
" Exploration of the structure-activity relationships of 4 led to the identification of a potent and orally bioavailable TRPM8 antagonist, tetrahydroisoquinoline 87."( Fused piperidines as a novel class of potent and orally available transient receptor potential melastatin type 8 (TRPM8) antagonists.
Bartberger, MD; Bo, Y; Chen, J; Correll, TL; Deng, H; Gavva, NR; Gore, V; Klionsky, L; Lehto, SG; Ma, V; Nishimura, N; Norman, MH; Tamayo, NA; Tang, P; Wang, W; Youngblood, B, 2012
)
"The objective of this study was to compare the bioavailability and tolerability of revaprazan and itopride combination therapy to those of equally dosed monotherapies to acquire basic drug-drug interaction information about revaprazan."( Bioavailability and tolerability of combination treatment with revaprazan 200 mg + itopride 150 mg: a randomized crossover study in healthy male Korean volunteers.
Bae, KS; Choi, HY; Jang, SB; Jin, SJ; Kim, MJ; Kim, YH; Lee, SJ; Lim, HS; Noh, YH; Sung, H, 2012
)
" Optimization of in vitro pharmocokinetic properties led to compound 25 exhibiting 52% bioavailability in mice and target engagement in an acute PK/PD study."( Preparation and optimization of new 4-(morpholin-4-yl)-(6-oxo-1,6-dihydropyrimidin-2-yl)amide derivatives as PI3Kβ inhibitors.
Abecassis, PY; Bonnevaux, H; Carry, JC; Certal, V; Delorme, C; Doerflinger, G; El-Ahmad, Y; Filoche-Rommé, B; Halley, F; Karlsson, A; Lengauer, C; Louboutin, A; Michot, N; Monget, S; Morales, R; Nicolas, JP; Perron, S; Schio, L; Thompson, F; Tric, B; Vade, I; Vincent, L; Virone-Oddos, A, 2012
)
" The starting point for the current study was inhibitor 2, which had high biochemical and antiviral potency but only moderate permeability in a Caco-2 assay and high B-to-A efflux, resulting in moderate rat bioavailability and low Cmax."( Identification of potent and orally bioavailable nucleotide competing reverse transcriptase inhibitors: in vitro and in vivo optimization of a series of benzofurano[3,2-d]pyrimidin-2-one derived inhibitors.
Bethell, R; Bousquet, Y; Cordingley, MG; DeRoy, P; Duan, J; Duplessis, M; Edwards, PJ; Garneau, M; Halmos, T; James, CA; Lamorte, L; Minville, J; Morency, L; Morin, S; Pelletier, A; Rajotte, D; Ribadeneira, M; Simoneau, B; Sturino, CF; Thavonekham, B; Tremblay, M; Tremblay, S, 2013
)
" Forodesine is an orally bioavailable PNP inhibitor with picomolar potency."( Preclinical and clinical evaluation of forodesine in pediatric and adult B-cell acute lymphoblastic leukemia.
Balakrishnan, K; Bantia, S; Franklin, A; Gandhi, V; Ravandi, F, 2013
)
"Trametinib is an orally bioavailable mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor with antineoplastic activity."( Trametinib: first global approval.
McCormack, PL; Wright, CJ, 2013
)
"In order to investigate the influence of drug physicochemical properties on bioavailability of water insoluble drug nanosuspensions, five drug nanosuspensions were prepared using high pressure homogenization."( Influence of drug physicochemical properties on absorption of water insoluble drug nanosuspensions.
Cheng, J; Cun, D; Fang, L; Li, W; Liu, J; Quan, P; Xiang, R; Zhang, Y, 2014
)
"The aim of this phase 1, single centre, open label study in four patients with solid tumours was to determine the absolute bioavailability of a 2 mg oral dose of trametinib."( Concomitant oral and intravenous pharmacokinetics of trametinib, a MEK inhibitor, in subjects with solid tumours.
Bauman, J; Fang, L; Henriquez, F; Ho, M; Leonowens, C; Morrison, RA; Orford, K; Ouellet, D; Pendry, C; Young, GC, 2014
)
"The least-squares mean (90% confidence interval) absolute bioavailability of trametinib (2 mg tablet) was 72."( Concomitant oral and intravenous pharmacokinetics of trametinib, a MEK inhibitor, in subjects with solid tumours.
Bauman, J; Fang, L; Henriquez, F; Ho, M; Leonowens, C; Morrison, RA; Orford, K; Ouellet, D; Pendry, C; Young, GC, 2014
)
"Trametinib absolute bioavailability was moderate to high, whereas first pass metabolism was low."( Concomitant oral and intravenous pharmacokinetics of trametinib, a MEK inhibitor, in subjects with solid tumours.
Bauman, J; Fang, L; Henriquez, F; Ho, M; Leonowens, C; Morrison, RA; Orford, K; Ouellet, D; Pendry, C; Young, GC, 2014
)
" AMG2850 is potent in vitro at rat TRPM8 (IC90 against icilin activation of 204 ± 28 nM), highly selective (>100-fold IC90 over TRPV1 and TRPA1 channels), and orally bioavailable (F po > 40 %)."( AMG2850, a potent and selective TRPM8 antagonist, is not effective in rat models of inflammatory mechanical hypersensitivity and neuropathic tactile allodynia.
Davis, C; Gavva, NR; Kerstein, PC; Lehto, SG; Stucky, CL; Wang, J; Wang, W; Weyer, AD; Wild, KD; Youngblood, BD; Zhang, M, 2015
)
"The current practice of calculating the specific absorption rate (SAR) relies on local temperature measurements made using temperature probes."( Evaluation of radiofrequency safety by high temperature resolution MR thermometry using a paramagnetic lanthanide complex.
Bansal, N; Dharmadhikari, S; James, JR; Nyenhuis, J, 2016
)
"Pirfenidone is an orally bioavailable synthetic compound with therapeutic potential for idiopathic pulmonary fibrosis."( XL413, a cell division cycle 7 kinase inhibitor enhanced the anti-fibrotic effect of pirfenidone on TGF-β1-stimulated C3H10T1/2 cells via Smad2/4.
Fu, ST; He, Y; Jin, SF; Liu, ZL; Ma, HL; Zhang, CP, 2015
)
" Pharmacokinetics in preclinical species characterized by low to moderate plasma clearances, good oral bioavailability at 3- to 5-mg/kg doses, and renal clearance as the projected major clearance mechanism in humans."( Pharmacokinetics and Disposition of the Thiouracil Derivative PF-06282999, an Orally Bioavailable, Irreversible Inactivator of Myeloperoxidase Enzyme, Across Animals and Humans.
Di, L; Dong, JQ; Feng, B; Kalgutkar, AS; Ryder, T; Sagawa, K; Terra, SG; Varma, MV; Wolford, A, 2016
)
" This open-label, two-period, two-treatment, randomized, crossover study assessed the relative bioavailability of the trametinib pediatric oral solution compared to the tablet formulation after a single-dose administration to adult patients with solid tumors."( Relative bioavailability of pediatric oral solution and tablet formulations of trametinib in adult patients with solid tumors.
Allred, A; Bendell, J; Burris, H; Cox, DS; Gordon, MS; Infante, JR; Jones, S; Orford, K; Zhou, Y, 2015
)
"Starting with a lead [1,5-a]pyrimidin-7(4H)-one-containing molecule (1), we generated potent, selective and orally bioavailable KDM5 inhibitors."( Lead optimization of a pyrazolo[1,5-a]pyrimidin-7(4H)-one scaffold to identify potent, selective and orally bioavailable KDM5 inhibitors suitable for in vivo biological studies.
Classon, M; Cummings, R; Deshmukh, G; Dragovich, PS; Gehling, VS; Gustafson, A; Harmange, JC; Kiefer, JR; Labadie, S; Lai, T; Liang, J; Liao, J; Liederer, BM; Liu, Y; Mao, W; Murray, L; Ortwine, DF; Trojer, P; Van der Porten, E; Vinogradova, M; Zhang, B; Zheng, X, 2016
)
"AZD3965, a pyrole pyrimidine derivative, is a potent and orally bioavailable inhibitor of monocarboxylate transporter 1 (MCT1), currently in a Phase I clinical trial in UK for lymphomas and solid tumors."( Development and validation of a liquid chromatography tandem mass spectrometry assay for AZD3965 in mouse plasma and tumor tissue: Application to pharmacokinetic and breast tumor xenograft studies.
Guan, X; Morris, ME; Ruszaj, D, 2018
)
" The enterohepatic circulation model reasonably captured the second peak of AZD3241, and high-fat food increased the absorption rate by 69%."( Population Pharmacokinetic Modeling With Enterohepatic Circulation for AZD3241 in Healthy Subjects and Patients With Multiple System Atrophy.
Al-Huniti, N; Li, J; Li, Y; Mullen, JA; Savage, A; Taylor, W; Tong, X; Xu, H; Zhou, D, 2018
)
"3-fold improved oral bioavailability in comparison with revaprazan powder."( Novel revaprazan-loaded gelatin microsphere with enhanced drug solubility and oral bioavailability.
Choi, HG; Din, FU; Jeong, SC; Jin, SG; Kim, DS; Kim, JO; Kim, JS; Oh, KT; Park, JH; Yong, CS; Youn, YS; Yousaf, AM, 2018
)
" The orally bioavailable 6-(3-chloro-5-methylphenyl)-3-(3-fluoro-5-hydroxyphenyl)-5-({methyl[(2S)-pyrrolidin-2-ylmethyl]amino}methyl)-3H,4H-pyrido[2,3-d]pyrimidin-4-one (36) also suppresses GH secretion in GHRH-challenged rats in a dose-dependent manner."( Discovery of substituted 3H-pyrido[2,3-d]pyrimidin-4-ones as potent, biased, and orally bioavailable sst2 agonist.
Betz, SF; Chen, Z; Kusnetzow, AK; Nguyen, J; Rico-Bautista, E; Struthers, RS; Tan, H; Zhao, J; Zhu, Y, 2020
)
"To enhance the oral bioavailability of revaprazan (RVP), a novel solid, supersaturable micelle (SSuM) was developed."( Development of a Solid Supersaturable Micelle of Revaprazan for Improved Dissolution and Oral Bioavailability Using Box-Behnken Design.
Choi, JY; Choi, YW; Goo, YT; Kim, CH; Kim, HK; Kim, MS; Sa, CK, 2021
)
"A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the dissolution and oral bioavailability (BA) of revaprazan (RVP)."( Enhanced dissolution and bioavailability of revaprazan using self-nanoemulsifying drug delivery system.
Choi, YW; Goo, YT; Kang, MJ; Kim, CH; Kim, HK; Kim, MS; Lee, S; Sa, CK; Sin, GH, 2022
)
" In this open-label, phase 1, single-dose, randomized, 2-treatment, 2-period crossover study in healthy volunteers, bioavailability of a single 2-mg tablet of trametinib containing 9% DMSO (test formulation), corresponding to the lowest DMSO content in the tablet after storage at 25°C for 36 months, was evaluated vs bioavailability of a 2-mg tablet containing 11% DMSO (reference formulation)."( Comparative Bioavailability of a Single Dose of Trametinib (TMT212) Containing 9% vs 11% Dimethyl Sulfoxide in Randomized Healthy Volunteers to Assess Long-Term Storage at Room Temperature.
Chiparus, O; Choudhury, S; Ilankumaran, P; Kim, C; Lau, M; Tan, EY; Ziltener, C, 2022
)
" However, orgovyx has demonstrated poor pharmacokinetic profile with low oral bioavailability and high efflux."( Discovery of the thieno[2,3-d]pyrimidine-2,4-dione derivative 21a: A potent and orally bioavailable gonadotropin-releasing hormone receptor antagonist.
Gao, Y; Jiang, W; Liu, C; Lu, J; Ma, M; Tian, J; Wang, W; Wang, Y; Ye, L; Yu, D; Zhang, J; Zhang, R; Zhao, M; Zou, F, 2022
)

Dosage Studied

ExcerptReference
" While pretreatment with inhaled AS-35 (1mg) did not affect the STA2 dose-response curve."( Interaction of thromboxane A2 and leukotrienes in guinea pig airways in vivo.
Bando, T; Fujimura, M; Matsuda, T; Mizuhashi, K, 1991
)
" Mild subjective adverse effects (dizziness, taste perversion, and circumoral paresthesia) which did not necessitate discontinuing the infusion occurred in the highest dosage group."( Pharmacokinetic and tolerance evaluation of actisomide, a new antiarrhythmic agent, in healthy volunteers.
Dean, RR; Destache, CJ; Hilleman, DE; Malesker, MA; Mohiuddin, SM; Sketch, MH; Stoysich, A, 1991
)
" The inhibition of wheal size was maximal by 2 hr after dosing and was present at 8 hr."( Temelastine, a new H1-receptor antagonist.
Alexander, F; Allison, N; Dubb, JW; Familiar, RG; Stote, RM; Tatoian, D, 1986
)
" In anaesthetized guinea-pigs SK&F 93944 displaced histamine bronchoconstriction dose-response curves at doses which had negligible effects on histamine tachycardia."( Pharmacological studies with SK&F 93944 (temelastine), a novel histamine H1-receptor antagonist with negligible ability to penetrate the central nervous system.
Brown, EA; Griffiths, R; Harvey, CA; Owen, DA, 1986
)
" The pharmacokinetics of antipyrine were assessed in eight male normal subjects after single oral doses of 10 mg/kg antipyrine, administered prior to chronic dosing with temelastine 100 mg twice daily for 2 weeks, and 48 hours after the last dose of temelastine."( Temelastine, a novel histamine H1-receptor antagonist, does not induce oxidative hepatic enzyme activity in man.
de Mey, C; Meineke, I; Wesche, H,
)
" This was apparent after a single dose of the compound and was reversible after dosing for 7 days."( Effects of toxic doses of a novel histamine (H2) antagonist on the rat thyroid gland.
Atterwill, CK; Brown, CG; Harland, RF; Major, IR, 1987
)
" The effectiveness of chronic dosing with temelastine (SK&F 93944) 75 mg twice daily and terfenadine 60 mg twice daily compared with placebo in inhibiting the weal and flare response to intradermal histamine was assessed using non-invasive objective assessment techniques."( Non-invasive instrumental techniques to detect terfenadine and temelastine induced suppression of histamine weals in man.
Marks, R; Shall, L, 1987
)
" Investigative studies showed evidence for marked and sustained hypergastrinemia increasing on chronic dosing which was capable of restoring gastric acid secretion and pH to near control values."( Gastric ECL-cell hyperplasia and carcinoids in rodents following chronic administration of H2-antagonists SK&F 93479 and oxmetidine and omeprazole.
Betton, GR; Buckley, P; Dormer, CS; Pert, P; Price, CA; Wells, T, 1988
)
" This protection was dependent upon the dosage of pyrimidinone administered."( Effect of pyrimidinone treatment on lethal and immunosuppressive murine cytomegalovirus infection.
Brideau, RJ; Wolcott, JA, 1985
)
" Mean inhibitions of MAO during the 4th h after dosing of SK&F 93479 were significant at all dose levels, and a significant effect could still be seen during the 26th h for the two oral doses."( Repeated pentagastrin-stimulated gastric acid secretory tests carried out in the evaluation of the pharmacodynamics of a new histamine H2-receptor antagonist, SK&F 93479.
Bodemar, G; Jönsson, KA; Norlander, B; Walan, A, 1984
)
" Forestomach lesions of marked focal hyperplasia and hyperkeratosis were observed at a 48% incidence after 1 year daily gavage dosing with 1000 mg/kg."( Pathology of the forestomach in rats treated for 1 year with a new histamine H2-receptor antagonist, SK&F 93479 trihydrochloride.
Betton, GR; Salmon, GK, 1984
)
" After block of desensitization by concanavalin-A, dose-response analysis for activation of kainate-preferring receptors in DRG neurons gave the potency sequence trifluoromethyl > iodo > bromo approximately chloro > nitro approximately cyano > kainate > methyl > fluoro > (R,S)-AMPA >> willardiine; EC50 values for the most and least potent willardiine derivatives, 5-trifluoromethyl (70 nM) and 5-fluoro (69 microM), differed 1000-fold."( Willardiines differentiate agonist binding sites for kainate- versus AMPA-preferring glutamate receptors in DRG and hippocampal neurons.
Jane, DE; Mayer, ML; Watkins, JC; Wong, LA, 1994
)
"A series of new 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e] pyrimidin-5-ones 3-substituted and/or 8,9-hydrogenated was prepared and tested for their diuretic, natriuretic and kaliuretic activities on male Wistar rats at a dosage of 25 mg/kg or less."( New 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidin-5-one derivatives as diuretics.
Martinez-Merino, V; Monge, A; Sanmartin, C; Simon, MA, 1995
)
" Moreover, the inhibitory effect of YM-14471 was more prolonged than those of famotidine and cimetidine by either route, and it was as long as that of omeprazole dosed orally."( Antisecretory effects of a novel and long-lasting histamine H2-receptor antagonist, YM-14471, in rats and dogs.
Fujihara, A; Kamato, T; Miyata, K; Nishida, A; Takeda, M; Yuki, H, 1993
)
" In the PAG/DR, the HA dose-response curve had an inverted U-shape, showing that HA can induce both antinociceptive (0."( Histamine-induced modulation of nociceptive responses.
Hough, LB; Mischler, SA; Nalwalk, JW; Thoburn, KK, 1994
)
" In experiment 3, explants were incubated in the presence of oxytocin or arginine vasopressin at 10(-9) to 10(-6) M to establish dose-response curves for the activation of PLC and release of PGF2 alpha."( Cellular mechanisms mediating the stimulation of ovine endometrial secretion of prostaglandin F2 alpha in response to oxytocin: role of phospholipase C and diacylglycerol.
Brockman, JA; Hayes, SH; Lee, JS; Lowberger, LL; Silvia, WJ; Trammell, DS, 1994
)
"2-Aryl-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-4-one derivatives having various substituents at the 4'-position, H or methyl at 1,3-positions and nitro or amino at 6-position were prepared and tested for their diuretic, natriuretic and kaliuretic activities on male Wistar rats at a dosage of 25 mg/kg or less."( New 2-aryl-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-4-one derivatives as diuretics.
Martinez-Merino, V; Monge, A; Sanmartin, C; Simon, MA, 1993
)
" Dramatic short term improvement is reported with the dosage regimen and complications."( Effects of preactivated MC540 in the treatment of lymphocytic plasmacytic stomatitis in feline leukemia virus and feline immunodeficiency virus positive cats.
Gulliya, KS; Lobprise, HB; Matthews, JL; Wiggs, RB, 1993
)
" Dose-response analysis yielded an apparent EC50 for R59022-induced oocyte maturation of approximately 15 microM."( Analysis of R59022 actions in Xenopus laevis oocytes.
Frith, T; Sadler, SE; Wasserman, WJ, 1996
)
" RO was nearly complete at 4 hr after dosing (98%) and remained elevated at 18 hr (46%)."( Positron emission tomographic analysis of central 5-hydroxytryptamine2 receptor occupancy in healthy volunteers treated with the novel antipsychotic agent, ziprasidone.
Alpert, NM; Babich, JW; Bonab, AA; Elmaleh, DR; Fischman, AJ; Rauch, SL; Rubin, RH; Shoup, TM; Williams, SA, 1996
)
" The dose-response curve for the three drugs was biphasic, suggesting that other mechanisms are operative at higher doses."( Pharmacological evaluation of IQM-95,333, a highly selective CCKA receptor antagonist with anxiolytic-like activity in animal models.
Ballaz, S; Barber, A; Del Río, J; Fortuño, A; García-López, MT; Gómez-Monterrey, I; González-Muñiz, R; Herranz, R; Martin-Martínez, M, 1997
)
" The dose-response curve of prolongation of ventricular effective refractory period produced by MS-551 was shifted significantly to the left compared with that induced by sotalol."( Electrophysiological effects of MS-551, a new class III agent: comparison with dl-sotalol in dogs.
Cui, G; Sakaguchi, Y; Sen, L; Singh, BN, 1998
)
" We investigated whether a Class III drug simply shifts the dose-response curve for defibrillation or more extensively alters the curve."( Effect of a class III antiarrhythmic drug on the configuration of dose response curve for defibrillation.
Kanese, Y; Murakawa, Y; Omata, M; Yamashita, T, 1999
)
"4 microg/ml mTHPC for 24 h incubation and then with 40 kJ/m2 light irradiation, whereas 40 microg/ml MC540 with 50 kJ/m2 light dosage was required to attain the same level of phototoxicity for NPC/HK1."( Photocytotoxic and DNA damaging effect of temoporfin (mTHPC) and merocyanine 540 (MC540) on nasopharyngeal carcinoma cell.
Chen, JY; Cheung, NH; Huang, DP; Lee, YL; Leung, AW; Mak, NK; Szeto, S; Yow, CM, 2000
)
" Previous studies have suggested that the AUC and C(max) of orally dosed YH1885 are dose-dependent in the range of 2 to 500 mg/kg."( The transport of a reversible proton pump antagonist, 5, 6-dimethyl-2-(4-Fluorophenylamino)-4-(1-methyl-1,2,3, 4-tetrahydroisoquinoline-2-yl) pyrimidine hydrochloride (YH1885), across caco-2 cell monolayers.
Chung, SJ; Kim, DC; Kim, HS; Lee, JW; Li, H; Shim, CK, 2001
)
" Information on each drug, such as the name of the drug, the dosage normally prescribed, and cost of treatment is listed."( What they say about: protease inhibitors.
,
)
" Progress is also highlighted about dosing regimens, antiretroviral resistance, and reconstitution of the immune system."( Moving forward: a treatment overview from the 12th World AIDS Conference.
Agosto, M, 1998
)
" The purpose of this study was to determine and compare the potencies of the alpha(1)-adrenoceptor antagonists terazosin, doxazosin, tamsulosin, and fiduxosin, based on relationships between plasma drug concentrations and blockade of phenylephrine (PE)-induced intraurethral (IUP) and mean arterial pressure (MAP) responses after single oral dosing in conscious male beagle dogs."( Modeling of relationships between pharmacokinetics and blockade of agonist-induced elevation of intraurethral pressure and mean arterial pressure in conscious dogs treated with alpha(1)-adrenoceptor antagonists.
Brune, ME; Hancock, AA; Hui, YH; Katwala, SP; Kerwin, JF; Marsh, KC; Meyer, MD; Milicic, I; Stolarik, D; Witte, DG, 2002
)
"Cimetidine co-administration produced an increase in sildenafil plasma levels; however, this increase is not sufficient to warrant dosage adjustment of either drug."( The effects of cimetidine and antacid on the pharmacokinetic profile of sildenafil citrate in healthy male volunteers.
Laboy, L; LeBel, M; Wilner, K, 2002
)
"Repeated dosing with erythromycin caused statistically significant increases in the AUC and Cmax of sildenafil (2."( The effects of steady-state erythromycin and azithromycin on the pharmacokinetics of sildenafil in healthy volunteers.
Faulkner, S; Harness, JA; Muirhead, GJ; Taubel, J, 2002
)
" Azithromycin did not affect the pharmacokinetics of sildenafil; therefore, no adjustment in dosage is necessary for patients receiving these drugs concomitantly."( The effects of steady-state erythromycin and azithromycin on the pharmacokinetics of sildenafil in healthy volunteers.
Faulkner, S; Harness, JA; Muirhead, GJ; Taubel, J, 2002
)
" Single once-daily oral doses of 30, 60, 90 or 120 mg of fiduxosin or placebo were administered to healthy elderly male subjects (n = 48; 8 active and 4 placebo per dosing group) for 14 consecutive days."( Multiple dose pharmacokinetics of fiduxosin under fasting conditions in healthy elderly male subjects.
Daszkowski, DJ; Dutta, S; Granneman, GR; Verlinden, M; Zhang, Y, 2002
)
" Single daily oral doses of 30, 60, or 90 mg of fiduxosin or placebo were administered to healthy adult male subjects (N = 36; 8 active and 4 placebo per dosing group) on Day 1 and Days 5 to 11 (7 consecutive days) after a high-fat breakfast."( Single- and multiple-dose pharmacokinetics of fiduxosin under nonfasting conditions in healthy male subjects.
Daszkowski, DJ; Dutta, S; Granneman, GR; Verlinden, M; Zhang, Y, 2002
)
"The steady-state pharmacokinetics and pharmacodynamics of two oral doses of lopinavir-ritonavir (lopinavir/r; 400/100 and 533/133 mg) twice daily (BID) when dosed in combination with efavirenz, plus two nucleoside reverse transcriptase inhibitors, were assessed in a phase II, open-label, randomized, parallel arm study in 57 multiple protease inhibitor-experienced but non-nucleoside reverse transcriptase inhibitor-naive human immunodeficiency virus (HIV)-infected subjects."( Pharmacokinetic-pharmacodynamic analysis of lopinavir-ritonavir in combination with efavirenz and two nucleoside reverse transcriptase inhibitors in extensively pretreated human immunodeficiency virus-infected patients.
Bernstein, B; Bertz, R; Brun, S; Foit, C; Granneman, GR; Hsu, A; Isaacson, J; Kempf, DJ; King, M; Lam, W; Richards, B; Rode, R; Rynkiewicz, K; Sun, E, 2003
)
"Paediatric solid tumours exhibit steep dose-response curves to alkylating agents and are therefore considered candidates for high-dose chemotherapy and autologous stem cell support."( Preferential inactivation of paediatric solid tumour cells by sequential exposure to Merocyanine 540-mediated photodynamic therapy and Edelfosine: implications for the ex vivo purging of autologous haematopoietic stem cell grafts.
Anderson, GS; Miyagi, K; Sampson, R; Sieber, F; Tsujino, I, 2003
)
" The pharmacokinetics of lopinavir did not appear to be dependent on age when dosing was based on body surface area but were decreased on coadministration with nevirapine."( Forty-eight-week evaluation of lopinavir/ritonavir, a new protease inhibitor, in human immunodeficiency virus-infected children.
Allen, U; Arpadi, S; Bernstein, B; Bertz, RJ; Cahn, P; Castrejón, MM; Chadwick, E; Deetz, CO; Gomez, P; Handelsman, E; Heuser, RS; Hsu, AF; Kempf, DJ; Pelton, S; Ramilo, O; Renz, CL; Rode, RA; Sáez-Llorens, X; Sun, E; Violari, A, 2003
)
" Column chromatography methodology was developed to separate lopinavir from ritonavir starting from the commercially available lopinavir-ritonavir combination dosage form."( Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir.
Greenblatt, DJ; Harmatz, JS; Hesse, LM; Richert, C; von Moltke, LL; Weemhoff, JL, 2003
)
" In this single-center, 7-day, prospective, double-blind, single-dose, crossover, parallel-group study, subjects were randomized to be bilaterally dosed with pemirolast, cromolyn, or ketorolac at each of 3 visits."( A combined analysis of two studies assessing the ocular comfort of antiallergy ophthalmic agents.
Amdahl, L; Graves, A; Shulman, DG; Washington, C, 2003
)
"This study examines the pharmacokinetic/pharmacodynamic interactions between (1) lopinavir-ritonavir (L/R), a fixed combination of protease inhibitors used for the treatment of HIV disease, and (2) ritonavir alone at the same dosage as that in the L/R formulation, with methadone, an opiate frequently used in substance abuse pharmacotherapy for opioid (heroin)-dependent injection drug users, many of whom are infected with HIV."( The protease inhibitor lopinavir-ritonavir may produce opiate withdrawal in methadone-maintained patients.
Friedland, G; Jatlow, P; McCance-Katz, EF; Rainey, PM, 2003
)
" Great caution is required in the management of tacrolimus dosage when Kaletra is introduced or withdrawn in HIV-positive patients after liver transplantation, particularly in the presence of hepatic dysfunction."( Effect of coadministered lopinavir and ritonavir (Kaletra) on tacrolimus blood concentration in liver transplantation patients.
Eghtesad, B; Fung, JJ; Jain, AB; Marcos, A; Rafail, AB; Ragni, M; Shapiro, R; Venkataramanan, R, 2003
)
" The volunteers were randomly allocated to single dose groups of 60 mg, 100 mg, 150 mg, 200 mg, and 300 mg (6 subjects per dose, including 2 placebos) or to multiple-dose groups of 150 mg and 300 mg (once-daily dosing for 7 days; 8 subjects per dose, including 2 placebos)."( Pharmacokinetic and pharmacodynamic evaluation of a novel proton pump inhibitor, YH1885, in healthy volunteers.
Bae, KS; Cho, JY; Chung, JY; Jang, IJ; Lim, HS; Moon, BS; Shin, SG; Shon, JH; Song, KS; Yi, SY; Yu, KS, 2004
)
" The aim of the study was to measure unbound plasma concentrations of lopinavir (LPV) and to relate them to the total plasma concentrations to establish the unbound percentage in vivo during a full dosage interval."( Lopinavir protein binding in vivo through the 12-hour dosing interval.
Back, DJ; Boffito, M; Bonora, S; Di Perri, G; Hoggard, PG; Khoo, SH; Lindup, WE; Sinicco, A, 2004
)
" The data suggest that daily dosing of > or =3 mg EMD 281014 should be sufficient to provide sustained high levels of 5HT2-receptor occupancy in future clinical trials."( EMD 281014, a specific and potent 5HT2 antagonist in humans: a dose-finding PET study.
Kapur, S; Mamo, D; Romach, MK; Sedman, E; Sellers, EM; Tillner, J, 2004
)
" A retrospective study carried out of 72 probable SARS patients has shown that cases who received pulse methylprendisolone did not differ in cumulative steroid dosage or adverse reactions, although the former patients had less oxygen requirement, better radiographic outcome, and less likelihood of requiring rescue pulse steroid therapy than their counterparts."( SARS: pharmacotherapy.
Tsang, K; Zhong, NS, 2003
)
" After 48 weeks, LPV/r was dosed open-label at 400/100 mg every 12 hours with stavudine and lamivudine."( Long-term safety and durable antiretroviral activity of lopinavir/ritonavir in treatment-naive patients: 4 year follow-up study.
Benson, C; Brun, SC; Eron, JJ; Gulick, RM; Hicks, C; Kessler, HA; King, KR; King, MS; Murphy, RL; White, AC, 2004
)
" The dosage of itraconazole was reduced when it was used in combination with lopinavir/ritonavir."( Drug-drug interaction between itraconazole and the antiretroviral drug lopinavir/ritonavir in an HIV-1-infected patient with disseminated histoplasmosis.
Beijnen, JH; Crommentuyn, KM; Huitema, AD; Mulder, JW; Schellens, JH; Sparidans, RW, 2004
)
" After studying 12-hour pharmacokinetic profiles in 3 HIV-positive patients after liver transplantation, we describe how dosing of cyclosporine A can be adjusted to maintain effective immunosuppressive drug levels on a daily dosing schedule when ritonavir-boosted indinavir or lopinavir-based antiretroviral therapy is given."( Management of drug-to-drug interactions between cyclosporine A and the protease-inhibitor lopinavir/ritonavir in liver-transplanted HIV-infected patients.
Michaelis, HC; Rockstroh, JK; Sauerbruch, T; Spengler, U; Sudhop, T; Türler, A; Vogel, M; Voigt, E; Wolff, M, 2004
)
" Management should be individualized to each patient; dosage or medication adjustments may be necessary."( Coadministration of lopinavir/ritonavir and phenytoin results in two-way drug interaction through cytochrome P-450 induction.
Bertz, RJ; Eron, JJ; Gaedigk, A; Kashuba, AD; Lim, ML; Min, SS; Robinson, M, 2004
)
" This placebo-controlled dose-escalation trial investigated 6 telbivudine daily dosing levels (25, 50, 100, 200, 400, and 800 mg/d); treatment was given for 4 weeks, with 12 weeks' follow-up."( A dose-finding study of once-daily oral telbivudine in HBeAg-positive patients with chronic hepatitis B virus infection.
Brown, NA; Chao, GC; Lai, CL; Lee, YM; Lim, SG; Lloyd, DM; Myers, MW; Yuen, MF; Zhou, XJ, 2004
)
" The tissue distribution of radioactivity was examined in rats dosed with [14C]lopinavir in combination with ritonavir."( Metabolism and disposition of the HIV-1 protease inhibitor lopinavir (ABT-378) given in combination with ritonavir in rats, dogs, and humans.
Denissen, JF; Grabowski, BA; Jayanti, VK; Johnson, MK; Kempf, DJ; Kumar, GN; Lee, RD; Marsh, KC; Roberts, SA; Sham, HL; Sun, E; Thomas, S; Uchic, J, 2004
)
" On oral dosing to rats, ritonavir was found to increase the exposure of lopinavir-derived radioactivity 13-fold."( Metabolism and disposition of the HIV-1 protease inhibitor lopinavir (ABT-378) given in combination with ritonavir in rats, dogs, and humans.
Denissen, JF; Grabowski, BA; Jayanti, VK; Johnson, MK; Kempf, DJ; Kumar, GN; Lee, RD; Marsh, KC; Roberts, SA; Sham, HL; Sun, E; Thomas, S; Uchic, J, 2004
)
" HIV type 1 (HIV-1)-infected patients receiving EFV or lopinavir-ritonavir (LPV/r) had 9 or 10 blood samples drawn over 8 to 24 h of a dosing interval at steady state before and after receiving 250 mg of VPA twice daily for 7 days."( Effects of valproic acid coadministration on plasma efavirenz and lopinavir concentrations in human immunodeficiency virus-infected adults.
Cruttenden, K; DiCenzo, R; Gelbard, H; Morse, G; Peterson, D; Riggs, G; Schifitto, G, 2004
)
" Therefore, we studied the plasma and intracellular (cell-associated) steady-state pharmacokinetics of this PI combination in a dosage of 400/100 mg twice daily in a non-randomized cohort of HIV-1-infected individuals."( The plasma and intracellular steady-state pharmacokinetics of lopinavir/ritonavir in HIV-1-infected patients.
Beijnen, JH; Crommentuyn, KM; Huitema, AD; Mairuhu, AT; Meenhorst, PL; Mulder, JW; van Gorp, EC, 2004
)
"In antiretroviral-experienced subjects with sustained viral suppression, dual therapy with NVP plus LPV/rtv at standard dosage was as potent and safe as standard-of-care HAART at 48 weeks of follow-up."( Lopinavir/ritonavir plus nevirapine as a nucleoside-sparing approach in antiretroviral-experienced patients (NEKA study).
Burger, D; Clotet, B; Côté, H; López, S; Martínez, E; Miró, O; Moltó, J; Montaner, J; Negredo, E; Puig, J; Rey-Joly, C; Ribalta, J; Ruiz, L; Salazar, J, 2005
)
"Pharmacokinetic studies rely on blood sampling at times relative to predefined dosing intervals."( Successful projection of the time course of drug concentration in plasma during a 1-year period from electronically compiled dosing-time data used as input to individually parameterized pharmacokinetic models.
Bertz, R; Mayer, S; Rode, R; Tousset, E; Urquhart, J; Vrijens, B, 2005
)
" The median (interquartile range) LPV AUC(0,24 h), maximum plasma concentration (C(max)) and concentration at the end of the dosing interval (C(24 h)) after am and pm dosing was, respectively, 143 (116-214) mg l(-1) h, 12."( Absence of circadian variation in the pharmacokinetics of lopinavir/ritonavir given as a once daily dosing regimen in HIV-1-infected patients.
Bourbeau, M; Cameron, DW; Garber, GE; Giguere, P; Seguin, I; van Heeswijk, RP, 2005
)
"No differences were observed in the pharmacokinetics of LPV/r after am or pm dosing with food, which suggests that this once daily combination, can be taken in the morning or evening."( Absence of circadian variation in the pharmacokinetics of lopinavir/ritonavir given as a once daily dosing regimen in HIV-1-infected patients.
Bourbeau, M; Cameron, DW; Garber, GE; Giguere, P; Seguin, I; van Heeswijk, RP, 2005
)
" The Phase I clinical study demonstrated that end-of-treatment virological response rates were better for telbivudine recipients at multiple dosing levels as compared with placebo patients."( Telbivudine: a new nucleoside analogue for the treatment of chronic hepatitis B.
Han, SH, 2005
)
" However, many of the available agents in this class suffer shortcomings, including poor tolerability, difficult dosing regimens, and variable drug concentrations which may lead to generation of viral resistance."( Safety and antiviral activity of lopinavir/ritonavir-based therapy in human immunodeficiency virus type 1 (HIV-1) infection.
Hicks, CB; Kaplan, SS, 2005
)
" However, many available agents suffer shortcomings that limit their clinical value, including adverse effects, difficult dosing requirements and rapid development of resistance."( Lopinavir/ritonavir in the treatment of human immunodeficiency virus infection.
Hicks, CB; Kaplan, SS, 2005
)
" The dosage was 50 mg/kg twice daily (bid) for saquinavir and 230/57."( Pharmacokinetics and 24-week efficacy/safety of dual boosted saquinavir/lopinavir/ritonavir in nucleoside-pretreated children.
Ananworanich, J; Bergshoeff, A; Burger, D; Engchanil, C; Hill, A; Kosalaraksa, P; Pancharoen, C; Ruxrungtham, K; Siangphoe, U, 2005
)
"Ritonavir dosed at 100 mg bid significantly increased the concentration of total cholesterol, LDL cholesterol, total/HDL cholesterol ratio and triglycerides and reduced HDL cholesterol concentration."( The effect of low-dose ritonavir monotherapy on fasting serum lipid concentrations.
Mashinter, LD; Roberts, SE; Shafran, SD, 2005
)
" No significant relationship was established between the presence or the daily dosage of saquinavir in the treatment and lopinavir population pharmacokinetic parameters."( No significant influence of saquinavir hard-gel capsule administration on pharmacokinetics of lopinavir in combination with ritonavir: a population approach.
Allavena, C; Dailly, E; Gagnieu, MC; Jolliet, P; Raffi, F, 2005
)
"To review available literature on the pharmacology, pharmacokinetics, dosing and administration, efficacy, and safety of the antiviral nucleoside analog telbivudine."( Telbivudine: a novel nucleoside analog for chronic hepatitis B.
Kim, JW; Louie, SG; Park, SH, 2006
)
" The Ccell/Ctot and Cu/Ctot ratio was unaffected by the addition of the second PI and remained stable throughout dosing interval."( Ritonavir-boosted atazanavir-lopinavir combination: a pharmacokinetic interaction study of total, unbound plasma and cellular exposures.
Biollaz, J; Buclin, T; Cavassini, M; Colombo, S; Decosterd, LA; Franc, C; Guignard, N; Khonkarly, M; Rochat, B; Tarr, PE; Telenti, A, 2006
)
" The clinical significance of this decrease is unknown and warrants further investigation to determine the need for tailoring LPV dosage in selected cases."( Ritonavir-boosted atazanavir-lopinavir combination: a pharmacokinetic interaction study of total, unbound plasma and cellular exposures.
Biollaz, J; Buclin, T; Cavassini, M; Colombo, S; Decosterd, LA; Franc, C; Guignard, N; Khonkarly, M; Rochat, B; Tarr, PE; Telenti, A, 2006
)
"Lopinavir/ritonavir is approved for treatment of HIV-infected children at a dosage regimen of 230/57."( Lopinavir/ritonavir exposure in treatment-naive HIV-infected children following twice or once daily administration.
Bassetti, M; Dentone, C; Di Biagio, A; Gatti, G; Gattinara, GC; Giaquinto, C; Martino, AM; Merlo, M; Rampon, O; Rosso, R; Viganò, A; Viscoli, C, 2006
)
" In both instances, the carbamazepine dosage was decreased by 33%, which resulted in resolution of symptoms."( Carbamazepine toxicity induced by lopinavir/ritonavir and nelfinavir.
Bates, DE; Herman, RJ, 2006
)
" Carbamazepine toxicity may be prevented by reducing the carbamazepine dosage by 25-50% when protease inhibitors are introduced."( Carbamazepine toxicity induced by lopinavir/ritonavir and nelfinavir.
Bates, DE; Herman, RJ, 2006
)
" The dosage level of piperidenafil in the herbal product was 41 mg per capsule when calculated as the free base."( Use of liquid chromatography-mass spectrometry and a hydrolytic technique for the detection and structure elucidation of a novel synthetic vardenafil designer drug added illegally to a "natural" herbal dietary supplement.
Reepmeyer, JC; Woodruff, JT, 2006
)
"The purpose of this study was to determine the pharmacokinetics and tolerability of three different indinavir and lopinavir/ritonavir dosing regimens."( Association of total bilirubin with indinavir and lopinavir plasma concentrations in HIV-infected patients receiving three different double-boosted dosing regimens.
Dicenzo, R; Larppanichpoonphol, P; Luque, A; Reichman, R, 2006
)
"HIV-infected adults receiving lopinavir/ritonavir 400/100 mg twice daily with food had nine plasma samples taken over a 12 h dosing interval at baseline (BL), after adding indinavir 600 mg twice daily for 10 days (R1), indinavir 800 mg twice daily for 5 days (R2) and lopinavir/ritonavir 533/133 mg plus indinavir 600 mg twice daily for 10 days (R3)."( Association of total bilirubin with indinavir and lopinavir plasma concentrations in HIV-infected patients receiving three different double-boosted dosing regimens.
Dicenzo, R; Larppanichpoonphol, P; Luque, A; Reichman, R, 2006
)
" Steady state was reached after daily dosing for 5 to 7 days."( Pharmacokinetics of telbivudine in healthy subjects and absence of drug interaction with lamivudine or adefovir dipivoxil.
Brown, NA; Chao, GC; Fielman, BA; Lloyd, DM; Zhou, XJ, 2006
)
" Once-daily dosing may offer an advantage to adherence."( Pharmacokinetics of a once-daily regimen of lopinavir/ritonavir in HIV-1-infected children.
Burger, D; de Groot, R; van der Lee, M; Verweel, G, 2006
)
" Further research, especially in young children, is necessary to determine whether a higher dosage of lopinavir/ritonavir once daily must be given to reach the target level for Cmin."( Pharmacokinetics of a once-daily regimen of lopinavir/ritonavir in HIV-1-infected children.
Burger, D; de Groot, R; van der Lee, M; Verweel, G, 2006
)
" Despite therapeutic drug monitoring and subsequent efavirenz dosage reductions, side-effects did not resolve completely and lopinavir concentrations remained relatively low."( Genotyping of CYP2B6 and therapeutic drug monitoring in an HIV-infected patient with high efavirenz plasma concentrations and severe CNS side-effects.
Hansen, AB; Justesen, US; Mathiesen, S; Von Lüttichau, HR, 2006
)
" Additional investigations are warranted to determine the optimal dosing of FPV with LPV/RTV."( Dose separation does not overcome the pharmacokinetic interaction between fosamprenavir and lopinavir/ritonavir.
Corbett, AH; Eron, JJ; Kalvass, LA; Kashuba, AD; Lim, ML; Ngo, LT; Patterson, KB; Tien, HC, 2006
)
" The consequences of these pharmacokinetic discrepancies and the necessity to modify the currently recommended dosage regimen should be further investigated."( Population analysis of weight-, age-, and sex-related differences in the pharmacokinetics of lopinavir in children from birth to 18 years.
Blanche, S; Chaix, ML; Delaugerre, C; Firtion, G; Hirt, D; Jullien, V; Macassa, E; Pons, G; Rey, E; Rouzioux, C; Teglas, JP; Tréluyer, JM; Urien, S; Vaz, P, 2006
)
" Despite high molecular weights, clogPs, and polar surface areas, the compounds are generally well absorbed and have excellent pharmacokinetic (PK) properties when dosed as sodium salts."( Potent, selective pyrimidinetrione-based inhibitors of MMP-13.
Antipas, AS; Berliner, MA; Datta, K; Downs, JT; Eskra, JD; Forman, MD; Freeman-Cook, KD; Greer, EM; Guzman, R; Hardink, JR; Janat, F; Jones, CS; Keene, NF; Laird, ER; Liras, JL; Lopresti-Morrow, LL; Martinelli, GJ; Mitchell, PG; Pandit, J; Reiter, LA; Robertson, D; Sperger, D; Vaughn-Bowser, ML; Waller, DM; Yocum, SA, 2006
)
" The pharmacokinetics, safety, and effectiveness of increased LPV/r dosing during the third trimester of pregnancy should be investigated."( Reduced lopinavir exposure during pregnancy.
Best, BM; Burchett, SK; Capparelli, E; Cotter, A; Elgie, C; Holland, DT; Hu, C; Mirochnick, M; Read, JS; Smith, E; Stek, AM; Tuomala, R, 2006
)
"Forty-two healthy adult male and female subjects 18-40 years of age were randomized into four telbivudine dosing groups of 200 mg, 400 mg, 600 mg and 800 mg."( [Study on the pharmacokinetic profile of telbivudine].
Brown, NA; Hu, P; Jiang, J; Shen, K; Wang, HY; Zhou, XJ, 2006
)
" The pharmaceutical development of SK3530 necessitated the availability of an assay for the quantification and purity determination of SK3530 active pharmaceutical ingredient (API) and its pharmaceutical dosage form."( Validation of a HPLC method for the quantification and purity determination of SK3530 in drug substance and tablet.
Chi, SC; Jang, WJ; Oh, JG, 2007
)
" After a regular oral dose of Kaletra (400 mg lopinavir, 100 mg ritonavir) analyte concentrations were detectable over a full dosing interval in plasma, ultrafiltrate, and PBMCs."( Monitoring of lopinavir and ritonavir in peripheral blood mononuclear cells, plasma, and ultrafiltrate using a selective and highly sensitive LC/MS/MS assay.
Burhenne, J; Ehrhardt, M; Haefeli, WE; Mikus, G; Möck, M, 2007
)
" Melt extrusion technology was used to produce a tablet formulation reducing the number of dosage units administered per day and simplifying storage requirements."( The tablet formulation of lopinavir/ritonavir provides similar bioavailability to the soft-gelatin capsule formulation with less pharmacokinetic variability and diminished food effect.
Awni, W; Breitenbach, J; Brun, SC; Chiu, YL; Doan, T; Hanna, GJ; Heuser, RS; Klein, CE; Morris, JB; Zhu, T, 2007
)
"Most antiretrovirals are metabolized in the liver, and lower dosing could be advisable in patients with severe liver insufficiency."( Influence of liver fibrosis stage on plasma levels of antiretroviral drugs in HIV-infected patients with chronic hepatitis C.
Barreiro, P; Gonzalez-Lahoz, J; Jiménez-Nácher, I; Labarga, P; Martín-Carbonero, L; Rodríguez-Novoa, S; Ruiz, A; Soriano, V, 2007
)
" The ATV area under the concentration-time curve from dosing to 24 hours after the dose (AUC0-24; GM: 36."( Beneficial pharmacokinetic interaction between atazanavir and lopinavir/ritonavir.
Agarwala, S; Barditch-Crovo, P; Carson, K; Flexner, C; Fuchs, E; Parsons, T; Pham, PA; Vasist, L, 2007
)
" Both 8-Br-cAMP (100 microM) and forskolin (10 microM) right-shifted the dose-response curves for the TRPM8-mediated effect of icilin and menthol on intracellular Ca(2+)."( Regulation of transient receptor potential channels of melastatin type 8 (TRPM8): effect of cAMP, cannabinoid CB(1) receptors and endovanilloids.
De Petrocellis, L; Di Marzo, V; Moriello, AS; Orlando, P; Starowicz, K; Vivese, M, 2007
)
" This coformulation was designed to overcome the problems of earlier agents of this class of drugs concerning unfavorable pharmacokinetics with a higher frequency of dosing and therapy failure."( Lopinavir/ritonavir: appraisal of its use in HIV therapy.
von Hentig, N, 2007
)
" The timing and dosage regimens of steroid in the treatment of SARS are controversial."( Pharmacologic treatment of SARS: current knowledge and recommendations.
Tai, DY, 2007
)
" Individuals established on ATV (300 mg and 100 mg ritonavir daily) or LPV (400 mg and 100 mg ritonavir twice daily)-containing regimens completed two clinical visits (trough and directly observed therapy) during which dosing characteristics, concomitant medication, and substance use were recorded."( Assessing the impact of substance use and hepatitis coinfection on atazanavir and lopinavir trough concentrations in HIV-infected patients during therapeutic drug monitoring.
Boston, NS; Brazeau, D; Catanzaro, L; DiFrancesco, R; Fischl, MA; Forrest, A; Gripshover, B; Ma, Q; Morse, GD; Reichman, RC; Slish, J; Zingman, BS, 2007
)
" When efavirenz (four patients) or a nucleoside analogue combination (one patient) was added, very little change in tacrolimus dosing was required."( Effect of highly active antiretroviral therapy on tacrolimus pharmacokinetics in hepatitis C virus and HIV co-infected liver transplant recipients in the ANRS HC-08 study.
Abbara, C; Barrail, A; Boissonnas, A; Bonhomme-Faivre, L; Duclos-Vallée, JC; Samuel, D; Taburet, AM; Teicher, E; Vincent, I; Vittecoq, D, 2007
)
" Tacrolimus dosing must be optimised according to therapeutic drug monitoring and the antiretroviral drug combination."( Effect of highly active antiretroviral therapy on tacrolimus pharmacokinetics in hepatitis C virus and HIV co-infected liver transplant recipients in the ANRS HC-08 study.
Abbara, C; Barrail, A; Boissonnas, A; Bonhomme-Faivre, L; Duclos-Vallée, JC; Samuel, D; Taburet, AM; Teicher, E; Vincent, I; Vittecoq, D, 2007
)
" These data indicate that chronic HIV treatment may be assisted with plasma concentration monitoring to identify those patients who may require dosage modification and/or regimen adjustment in order to optimize antiretroviral effects."( Factors associated with altered pharmacokinetics in substance users and non-substance users receiving lopinavir and atazanavir.
Boston, N; Brazeau, D; Catanzaro, LM; DiFrancesco, R; Fischl, MA; Forrest, A; Gripshover, B; Higgins, N; Lliguicota, F; Ma, Q; Morse, GD; Reichman, RC; Slish, J; Tooley, K; Zingman, BS,
)
"55 microM after oral dosing of mirodenafil (100 mg) in male volunteers."( Identification of cytochrome P450 enzymes responsible for N -dealkylation of a new oral erectogenic, mirodenafil.
Im, GJ; Jang, IJ; Ji, HY; Kim, SY; Lee, HS; Lee, SM; Park, EJ, 2008
)
"We assessed the safety and efficacy and evaluated the adherence to lopinavir/ritonavir (LPV/r) dosed QD or BID in antiretroviral-naive, HIV-1-infected subjects through 96 weeks of treatment."( A lopinavir/ritonavir-based once-daily regimen results in better compliance and is non-inferior to a twice-daily regimen through 96 weeks.
Domingo, P; Hairrell, JM; Hanna, GJ; Johnson, MA; King, MS; Molina, JM; Myers, R; Podsadecki, TJ; Rode, RA; Wilkin, A, 2007
)
" Rosuvastatin and lopinavir/ritonavir should be used with caution until the safety, efficacy, and appropriate dosing of this combination have been demonstrated in larger populations."( Drug/Drug interaction between lopinavir/ritonavir and rosuvastatin in healthy volunteers.
Flynn, DM; Gerber, JG; Hoody, DW; Kiser, JJ; Predhomme, JA; Wolfe, P, 2008
)
" An extensive SAR study led to sulfamide (R)- 22b, which inhibited the strand transfer with an IC50 of 7 nM and HIV infection in MT4 cells with a CIC95 of 44 nM, and ketoamide (S)- 28c that inhibited strand transfer with an IC50 of 12 nM and the HIV infection in MT4 cells with a CIC95 of 13 nM and exhibited a good pharmacokinetic profile when dosed orally to preclinical species."( Design and synthesis of bicyclic pyrimidinones as potent and orally bioavailable HIV-1 integrase inhibitors.
Crescenzi, B; Di Marco, A; Donghi, M; Felock, PJ; Ferrara, M; Fiore, F; Fonsi, M; Gardelli, C; Gonzalez-Paz, O; Kinzel, O; Laufer, R; Monteagudo, E; Muraglia, E; Nizi, E; Orvieto, F; Pescatore, G; Rowley, M; Summa, V, 2008
)
" The incidence of HCC correlated with serum HBV DNA level at entry in a dose-response relationship."( Active antiviral therapy for chronic hepatitis B and hepatocellular carcinoma.
Hann, HW, 2008
)
" From days 6-15, volunteers were randomized to receive lopinavir/ritonavir tablets dosed as either 600/150 or 800/200 mg twice daily, both in addition to 600 mg rifampicin once daily."( High incidence of adverse events in healthy volunteers receiving rifampicin and adjusted doses of lopinavir/ritonavir tablets.
Aarnoutse, RE; Boeree, MJ; Burger, DM; Koopmans, PP; L'homme, RF; Nijland, HM; Rongen, GA; van Crevel, R; van Uden, P, 2008
)
" Axonopathy in the sciatic nerves and in the spinal cords of monkeys dosed at 1,000 mg/kg/day observed in a 9-month study was considered equivocal, as the role of telbivudine in the injury could not be determined."( Nonclinical safety profile of telbivudine, a novel potent antiviral agent for treatment of hepatitis B.
Bridges, EG; Luo, S; Selden, JR, 2008
)
"Fifty children at 2 sites in Thailand were treated with standard dosing of SQV and LPV/r."( Double boosted protease inhibitors, saquinavir, and lopinavir/ritonavir, in nucleoside pretreated children at 48 weeks.
Ananworanich, J; Boonrak, P; Bunupuradah, T; Burger, D; Engchanil, C; Intasan, J; Kosalaraksa, P; Lumbiganon, P; Ruxrungtham, K; Schutz, M, 2008
)
" The convenient procedure for use and dosage of dry HCl for the reaction was elaborated and adapted for semiautomated solution-phase parallel synthesis."( Dry HCl in parallel synthesis of fused pyrimidin-4-ones.
Bogolubsky, AV; Plaskon, AS; Ryabukhin, SV; Stetsenko, SV; Tolmachev, AA; Volochnyuk, DM,
)
"The pharmacokinetics of EFV and LPV/RTV in hemodialysis suggests that no dosing adjustments are necessary in treatment-naive patients."( The pharmacokinetics and pharmacogenomics of efavirenz and lopinavir/ritonavir in HIV-infected persons requiring hemodialysis.
Amorosa, V; Cramer, YS; Gupta, SK; Hall, SD; Koletar, SL; Rosenkranz, SL; Szczech, LA, 2008
)
" Further exploration of regimens and dosing of antiretrovirals for children in these settings is needed."( Two-year outcomes of children on non-nucleoside reverse transcriptase inhibitor and protease inhibitor regimens in a South African pediatric antiretroviral program.
Berrisford, AE; Boulle, AM; Jaspan, HB, 2008
)
"Use of standard adult lopinavir/ritonavir (LPV/RTV) dosing (400/100 mg) during the third trimester of pregnancy results in reduced LPV exposure."( Lopinavir exposure with an increased dose during pregnancy.
Best, BM; Burchett, SK; Capparelli, E; Gaddipati, S; Holland, DT; Hu, C; Mirochnick, M; Read, JS; Smith, E; Stek, AM, 2008
)
" These data suggest that the higher LPV/RTV dose should be used in third trimester pregnant women; that it should be considered in second trimester pregnant women, especially those who are protease inhibitor experienced; and that postpartum LPV/RTV dosing can be reduced to standard dosing by 2 weeks after delivery."( Lopinavir exposure with an increased dose during pregnancy.
Best, BM; Burchett, SK; Capparelli, E; Gaddipati, S; Holland, DT; Hu, C; Mirochnick, M; Read, JS; Smith, E; Stek, AM, 2008
)
" Three different dosing regimens of elvucitabine were administered with lopinavir-ritonavir to 24 subjects with moderate levels of HIV."( Multiple-dose pharmacokinetic behavior of elvucitabine, a nucleoside reverse transcriptase inhibitor, administered over 21 days with lopinavir-ritonavir in human immunodeficiency virus type 1-infected subjects.
Colucci, P; Ducharme, MP; Hoepelman, IM; Pottage, JC; Robison, H; Schürmann, D; Turgeon, J, 2009
)
" These values were lower compared with the half-life over the respective dosing intervals (7."( Pharmacokinetics of atazanavir/ritonavir once daily and lopinavir/ritonavir twice and once daily over 72 h following drug cessation.
Back, D; Boffito, M; Else, L; Gazzard, B; Khoo, S; Moyle, G; Pozniak, A; Sousa, M; Taylor, J, 2008
)
" No evidence is available to guide dosing of lopinavir/ritonavir in tablet formulation in this setting."( Lopinavir/ritonavir pharmacokinetics in a substitution of high-dose soft-gelatin capsule to tablet formulation.
Guillemi, S; Harrigan, PR; Harris, M; Hull, MW; Lima, V; Montaner, JS, 2009
)
"The tablet formulation could probably result in improved lopinavir dosing and increases the feasibility of once-daily lopinavir/ritonavir-based regimens in children."( Pharmacokinetics of lopinavir in HIV type-1-infected children taking the new tablet formulation once daily.
Burger, DM; Driessen, GJ; Hartwig, NG; van der Flier, M; van der Knaap, LC; van der Lee, M; van Jaarsveld, P; Verweel, G, 2008
)
" We have some theoretical and clinical data available that enables us to consider the possibility of administering DRV/r once a day in some patients with a few mutations in the protease and in those where this dosing regime is considered important."( [Darunavir as first-line therapy. The TITAN study].
Curran, A; Ribera Pascuet, E, 2008
)
"A total of 191 patients were randomized 2:2:2:1 to one of three APL dosing regimens or to lamivudine (3TC)/zidovudine (ZDV) twice daily (bid), each in combination with lopinavir/ritonavir (LPV/r) 400 mg/100 mg bid."( Antiviral activity and safety of aplaviroc, a CCR5 antagonist, in combination with lopinavir/ritonavir in HIV-infected, therapy-naïve patients: results of the EPIC study (CCR100136).
Adkison, KK; Berger, D; Bonny, T; Cimoch, P; Lamarca, A; Lazzarin, A; Madison, SJ; McCarty, D; Millard, J; Nichols, WG; Salvato, P; Smaill, FM; Teofilo, E; Yeni, P, 2009
)
" Study M05-730 compared LPV/r tablets dosed once daily vs."( A once-daily lopinavir/ritonavir-based regimen is noninferior to twice-daily dosing and results in similar safety and tolerability in antiretroviral-naive subjects through 48 weeks.
Bernstein, B; Cohen, DE; da Silva, BA; Fredrick, L; Gathe, J; Gibbs, S; Loutfy, MR; Marsh, T; Naylor, C; Podzamczer, D; Rubio, R, 2009
)
" Safety and tolerability of once-daily and twice-daily dosing was also comparable."( A once-daily lopinavir/ritonavir-based regimen is noninferior to twice-daily dosing and results in similar safety and tolerability in antiretroviral-naive subjects through 48 weeks.
Bernstein, B; Cohen, DE; da Silva, BA; Fredrick, L; Gathe, J; Gibbs, S; Loutfy, MR; Marsh, T; Naylor, C; Podzamczer, D; Rubio, R, 2009
)
" We report the pharmacokinetics of standard LPV-ritonavir dosing (400/100 mg twice daily) in the immediate and early postpartum period when initiated during labor."( Early postpartum pharmacokinetics of lopinavir initiated intrapartum in Thai women.
Achalapong, J; Chotivanich, N; Cressey, TR; Jourdain, G; Maupin, R; Mirochnick, M; Prommas, S; Puthanakit, T; Roongpisuthipong, A; Shapiro, DE; Smith, E; Van Dyke, R; Yuthavisuthi, P, 2009
)
" Statistical analyses were performed on pharmacokinetic parameters: the area under the concentration-time curve from 0 to 4 h (AUC(0-4)), the maximum concentration of the drug (C(max)), and the residual concentration of the drug at the end of the dosing interval (C(trough)) for plasma and the AUC(0-4) and C(trough) for intracellular data."( Pilot pharmacokinetic study of human immunodeficiency virus-infected patients receiving tenofovir disoproxil fumarate (TDF): investigation of systemic and intracellular interactions between TDF and abacavir, lamivudine, or lopinavir-ritonavir.
Ayen, R; Clotet, B; Grassi, J; Levi, M; Negredo, E; Pruvost, A; Puig, J; Théodoro, F, 2009
)
" However, oxymethylphosphate (OMP) and oxyethylphosphate (OEP) prodrugs provided improved rates of cleavage, high levels of aqueous solubility, and high plasma levels of the parent drugs when dosed orally in rats and dogs."( Water-soluble prodrugs of the human immunodeficiency virus protease inhibitors lopinavir and ritonavir.
DeGoey, DA; Flosi, WJ; Grampovnik, DJ; Kati, WM; Kempf, DJ; Klein, LL; Liu, Y; Long, MA; Marsh, KC; McDaniel, KF; Molla, A; Wang, XC, 2009
)
" The final model was applied to simulate steady-state exposure for patients with impaired renal function for various dosing regimens."( Population pharmacokinetics of telbivudine and determination of dose adjustment for patients with renal impairment.
Farrell, C; Ke, J; Mayers, DL; Pentikis, HS; Sallas, WM; Zhou, XJ, 2009
)
"In total, 50 children from two sites in Thailand were treated with standard dosing of SQV and LPV/r."( Safety and efficacy of a double-boosted protease inhibitor combination, saquinavir and lopinavir/ritonavir, in pretreated children at 96 weeks.
Ananworanich, J; Boonrak, P; Bunupuradah, T; Burger, D; Engchanil, C; Kosalaraksa, P; Lumbiganon, P; Mahanontharit, A; Mengthaisong, T; Puthanakit, T; Ruxrungtham, K; Tompkins, E; van der Lugt, J, 2009
)
"This study suggests that the pharmacokinetics of lopinavir after twice-daily and once-daily dosing are similar, with no observable difference in tolerability, in this group of patients between 5 and 15 years old."( Pharmacokinetics and tolerability of once- versus twice-daily lopinavir/ritonavir treatment in HIV-1-infected children.
la Porte, C; Mitchell, CD; Parker, J; Rongkavilit, C; van Heeswijk, R; Zhang, G, 2009
)
"A total of 136 antiretroviral-naïve patients, with a CD4 cell count above 100 cells/microL and a plasma HIV RNA below 100,000 HIV-1 RNA copies/mL, were randomized and dosed with either lopinavir/ritonavir monotherapy (n = 83) or lopinavir/ritonavir + zidovudine/lamivudine (n = 53)."( Long-term (96-week) follow-up of antiretroviral-naïve HIV-infected patients treated with first-line lopinavir/ritonavir monotherapy in the MONARK trial.
Chaix, ML; Cohen-Codar, I; Delfraissy, JF; Dellamonica, P; Flandre, P; Ghosn, J; Girard, PM; Ngovan, P; Norton, M; Raffi, F, 2010
)
"An intravenous bolus injection and subsequent continuous infusion of NIF at a relatively low dosage were effective in treating severe ventricular tachyarrhythmias complicating ACS, reducing the potential risk of proarrhythmia."( Effects of intravenous nifekalant as a lifesaving drug for severe ventricular tachyarrhythmias complicating acute coronary syndrome.
Abe, A; Ikeda, T; Ishiguro, H; Mera, H; Miwa, Y; Miyakoshi, M; Shimizu, H; Tsukada, T; Yoshino, H; Yusu, S, 2009
)
"Virologically controlled patients treated with lopinavir/ritonavir were included in a 48 week pilot trial during which lopinavir/ritonavir dosage was reduced if lopinavir concentration was >5000 ng/mL at inclusion."( Impact of reduced dosing of lopinavir/ritonavir in virologically controlled HIV-infected patients: the Kaledose trial.
Girard, PM; Lacombe, K; Meynard, JL; Morand-Joubert, L; Poirier, JM; Slama, L; Valantin, MA, 2010
)
"This pilot study evaluating the biochemical and virological impact of a reduced dosing of lopinavir/ritonavir suggests that lower exposure to lopinavir/ritonavir could be associated with a significant decrease in triglycerides during treatment, without occurrence of resistance mutations that might impact the virological response to treatment."( Impact of reduced dosing of lopinavir/ritonavir in virologically controlled HIV-infected patients: the Kaledose trial.
Girard, PM; Lacombe, K; Meynard, JL; Morand-Joubert, L; Poirier, JM; Slama, L; Valantin, MA, 2010
)
" Each subject had 8 plasma lopinavir concentrations determined over a 12-hour dosing interval and 1 CSF lopinavir C(trough) value determined at the end of the study."( Lopinavir cerebrospinal fluid steady-state trough concentrations in HIV-infected adults.
Cruttenden, K; DiCenzo, R; DiFrancesco, R; Donnelly, J; Schifitto, G, 2009
)
"In this case, dosing recommendations of itraconazole 200 mg daily with lopinavir/ritonavir were appropriate."( Drug-drug interaction between itraconazole and the protease inhibitor lopinavir/ritonavir.
Hills-Nieminen, C; Houston, S; Hughes, CA; Shafran, SD, 2009
)
"The dose of itraconazole was reduced to 200 mg daily as recommended by current guidelines, and therapeutic drug monitoring of both itraconazole and lopinavir concentrations confirmed that no further dosage adjustments were necessary."( Drug-drug interaction between itraconazole and the protease inhibitor lopinavir/ritonavir.
Hills-Nieminen, C; Houston, S; Hughes, CA; Shafran, SD, 2009
)
"LPV/r dosed QD resulted in increased treatment adherence and was as efficacious as BID LPV/r while providing similar safety, tolerability, and limited resistance evolution."( Similar safety and efficacy of once- and twice-daily lopinavir/ritonavir tablets in treatment-experienced HIV-1-infected subjects at 48 weeks.
Andrade-Villanueva, J; Badal-Faesen, S; Bernstein, BM; Fredrick, LM; Gathe, J; Gaultier, IA; Mingrone, H; Podsadecki, TJ; Woodward, WC; Zajdenverg, R, 2010
)
" To compare efficacy of once-daily (QD) versus twice-daily (BID) antiretroviral therapy, we randomized human immunodeficiency virus (HIV)-positive, treatment-naive patients to lopinavir-ritonavir (LPV/r) administered at a dosage of 400 mg of lopinavir and 100 mg of ritonavir BID (n = 160) or 800 mg of lopinavir and 200 mg of ritonavir QD (n = 161), plus either emtricitabine 200 mg QD and extended-release stavudine at a dosage of 100 mg QD or tenofovir at a dosage of 300 mg QD."( Comparison of once-daily versus twice-daily combination antiretroviral therapy in treatment-naive patients: results of AIDS clinical trials group (ACTG) A5073, a 48-week randomized controlled trial.
Aberg, J; Andrade, A; Dehlinger, M; Eshleman, SH; Ferguson, E; Flexner, C; Gross, R; Kashuba, A; Kmack, A; Lalama, C; Mildvan, D; Parsons, T; Rosenkranz, SL; Sanne, I; Tierney, C, 2010
)
" A total of 82% of subjects completed the study, and 71% continued to receive the initially assigned dosage schedule."( Comparison of once-daily versus twice-daily combination antiretroviral therapy in treatment-naive patients: results of AIDS clinical trials group (ACTG) A5073, a 48-week randomized controlled trial.
Aberg, J; Andrade, A; Dehlinger, M; Eshleman, SH; Ferguson, E; Flexner, C; Gross, R; Kashuba, A; Kmack, A; Lalama, C; Mildvan, D; Parsons, T; Rosenkranz, SL; Sanne, I; Tierney, C, 2010
)
" These data suggest that 2 tablets of lopinavir-ritonavir BD may be inadequate when dosed with NNRTIs in Ugandan adults, and the dosage should be increased by the addition of an additional adult tablet or a half-dose tablet (100/25 mg), where available."( Pharmacokinetics of lopinavir-ritonavir with and without nonnucleoside reverse transcriptase inhibitors in Ugandan HIV-infected adults.
Dickinson, L; Gibb, DM; Gilks, CF; Kayiwa, J; Khoo, S; Kityo, C; Lutwama, F; Munderi, P; Nalumenya, R; Reid, A; Ssali, F; Tumukunde, D; Walker, AS, 2010
)
" Forodesine has biologic activity in CLL; pharmacodynamic parameters suggest that an alternate dosing schedule and/or higher doses to achieve greater intracellular dGTP may be beneficial in this patient population."( Phase 2 and pharmacodynamic study of oral forodesine in patients with advanced, fludarabine-treated chronic lymphocytic leukemia.
Balakrishnan, K; Bantia, S; Bickel, S; Chen, Y; Gandhi, V; Kantarjian, H; Keating, MJ; Kilpatrick, JM; O'Brien, S; Ravandi, F; Tyler, BF; Verma, D, 2010
)
" No dosage adjustment for S/GSK1349572 is required when used with lopinavir/ritonavir or darunavir/ritonavir."( The effect of lopinavir/ritonavir and darunavir/ritonavir on the HIV integrase inhibitor S/GSK1349572 in healthy participants.
Borland, J; Chen, S; Ishibashi, T; Lou, Y; Min, SS; Patel, P; Piscitelli, SC; Song, I, 2011
)
" Lopinavir CL/F increased linearly during the dosing interval."( Population pharmacokinetics of lopinavir in combination with rifampicin-based antitubercular treatment in HIV-infected South African children.
Elsherbiny, D; Maartens, G; McIlleron, H; Ren, Y; Simonsson, US, 2010
)
" The time-dependent lopinavir CL/F might be due to a time-dependent recovery from ritonavir inhibition of lopinavir metabolism during the dosing interval."( Population pharmacokinetics of lopinavir in combination with rifampicin-based antitubercular treatment in HIV-infected South African children.
Elsherbiny, D; Maartens, G; McIlleron, H; Ren, Y; Simonsson, US, 2010
)
" Postpartum dosing can be reduced to standard dosing before 2 weeks postpartum."( Lopinavir tablet pharmacokinetics with an increased dose during pregnancy.
Best, BM; Burchett, SK; Capparelli, EV; Hu, C; Li, H; Mirochnick, M; Read, JS; Rossi, SS; Smith, E; Stek, AM, 2010
)
" Buprenorphine/naloxone and LPV/r can be safely coadministered without need for dosage modification."( Pharmacokinetic interactions between buprenorphine/naloxone and once-daily lopinavir/ritonavir.
Altice, FL; Andrews, L; Bruce, RD; Fang, WB; Friedland, GH; Lin, SN; Ma, Q; Moody, DE; Morse, GD, 2010
)
" Emergence of postbaseline resistance mutations occurred at similar low rates in each dosing group."( Short communication: Comparable safety and efficacy with once-daily versus twice-daily dosing of lopinavir/ritonavir tablets with emtricitabine + tenofovir DF in antiretroviral-naïve, HIV type 1-infected subjects: 96 week final results of the randomized t
Bernstein, B; Cohen, D; da Silva, B; Fredrick, L; González-García, J; Johnson, M; Naylor, C; Sloan, L, 2010
)
" Coadministration with LPV/r resulted in a 51% decrease in steady-state area under plasma concentration-time curve from 0 to 12 hours (AUC(0-12,ss)) and steady-state maximum measured plasma concentration over a dosing interval (C(max,ss)) and a 50% decrease in steady-state plasma concentration 12 hours post last dosing (C(12,ss)) for BILR 355."( Coadministration with lopinavir and ritonavir decreases exposure to BILR 355, a nonnucleoside reverse transcriptase inhibitor, in healthy volunteers.
Berger, F; Castles, MA; Huang, DB; Huang, F; MacGregor, TR; Robinson, P; Scholl, P; Vinisko, R, 2011
)
" Conclusions The above target concentrations achieved in the majority of women and similarities in the fu% suggest standard dosing of the LPV/r tablet is appropriate during pregnancy."( Therapeutic drug monitoring of lopinavir/ritonavir in pregnancy.
Back, DJ; Boyle, N; Breiden, J; Brennan, M; Connor, EO; Coulter-Smith, S; Dickinson, L; Else, LJ; Fleming, C; Gibbons, S; Jackson, V; Khoo, SH; Lambert, JS, 2011
)
" Healthy volunteer studies have demonstrated a decrease in glucose disposal associated with dosing with specific antiretrovirals."( Effect of boosted fosamprenavir or lopinavir-based combinations on whole-body insulin sensitivity and lipids in treatment-naive HIV-type-1-positive men.
Back, DJ; Boffito, M; Jackson, AG; Mandalia, S; Moyle, GJ; Randell, PA; Taylor, J; Tjia, JF, 2010
)
" In xenografted tumor models, GSK1120212 orally dosed once daily had a long circulating half-life and sustained suppression of p-ERK1/2 for more than 24 hours; GSK1120212 also reduced tumor Ki67, increased p27(Kip1/CDKN1B), and caused tumor growth inhibition in multiple tumor models."( GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition.
Annan, R; Bleam, MR; Erskine, S; Fisher, KE; Gilmartin, AG; Groy, A; Kulkarni, SG; Laquerre, SG; Minthorn, EA; Moss, KG; Rominger, CM; Sutton, D; Yang, J; Zappacosta, F, 2011
)
" Initial TDM results prompted dosage change in 10% and assessment of adherence and/or pharmacist review in 11%."( Utility of therapeutic drug monitoring in the management of HIV-infected pregnant women in receipt of lopinavir.
Caswell, RJ; Chaponda, M; Ghanem, M; Gibbons, S; Jackson, V; Khoo, SH; Lambert, JS; Phillips, D; Poulton, M; Taylor, GP; Welch, J, 2011
)
" MK-1775, when dosed with GEM, abrogated the checkpoint arrest to promote mitotic entry and facilitated tumor cell death as compared to control and GEM-treated tumors."( MK-1775, a potent Wee1 inhibitor, synergizes with gemcitabine to achieve tumor regressions, selectively in p53-deficient pancreatic cancer xenografts.
Brooks, D; De Oliveira, E; Demuth, T; Hidalgo, M; Hirai, H; Maitra, A; Mizuarai, S; Ottenhof, N; Rajeshkumar, NV; Shumway, SD; Watters, J, 2011
)
"Nonlinear mixed-effects modeling was applied to explore the relationship between lopinavir and ritonavir concentrations over 72 h following drug cessation and also to assess other lopinavir and ritonavir dosing strategies compared to the standard 400-mg-100-mg twice-daily dose."( Sequential population pharmacokinetic modeling of lopinavir and ritonavir in healthy volunteers and assessment of different dosing strategies.
Aarons, L; Back, D; Boffito, M; Davies, G; Dickinson, L; Else, L; Khoo, S; Moyle, G; Pozniak, A; von Hentig, N, 2011
)
" We aimed at determining the optimal dosing regimen in neonates and infants weighing 1 to 10."( Lopinavir/ritonavir population pharmacokinetics in neonates and infants.
Anderson, ST; Blanche, S; Faye, A; Firtion, G; Giraud, C; Hirt, D; Khoo, S; Leprevost, M; Lyall, H; Peytavin, G; Solas, C; Thuret, I; Tréluyer, JM; Urien, S, 2011
)
" Based upon trough concentration limitations, suggested LPV/r dosing regimens were 40 mg 12 h(-1), 80 mg 12 h(-1) and 120 mg 12 h(-1) in the 1-2 kg, 2-6 kg and 6-10 kg group, respectively."( Lopinavir/ritonavir population pharmacokinetics in neonates and infants.
Anderson, ST; Blanche, S; Faye, A; Firtion, G; Giraud, C; Hirt, D; Khoo, S; Leprevost, M; Lyall, H; Peytavin, G; Solas, C; Thuret, I; Tréluyer, JM; Urien, S, 2011
)
"To describe laboratory abnormalities among HIV-infected women and their infants with standard and increased lopinavir/ritonavir (LPV/r) dosing during the third trimester of pregnancy."( Lopinavir/ritonavir dosing during pregnancy in Brazil and maternal/infant laboratory abnormalities.
Ceriotto, M; João, EC; Kreitchmann, R; Melo, VH; Mussi-Pinhata, MM; Peixoto, MF; Pilotto, JH; Read, J; Souza, Rda S; Stoszek, SK,
)
"164 women received LPV/r standard dosing [(798/198 or 800/200 mg/day) (Group 1)] and 70 increased dosing [(> 800/200 mg/day) (Group 2)]."( Lopinavir/ritonavir dosing during pregnancy in Brazil and maternal/infant laboratory abnormalities.
Ceriotto, M; João, EC; Kreitchmann, R; Melo, VH; Mussi-Pinhata, MM; Peixoto, MF; Pilotto, JH; Read, J; Souza, Rda S; Stoszek, SK,
)
" Increased LPV/r dosing during the third trimester of pregnancy appears to be safe for HIV-infected women and their infants."( Lopinavir/ritonavir dosing during pregnancy in Brazil and maternal/infant laboratory abnormalities.
Ceriotto, M; João, EC; Kreitchmann, R; Melo, VH; Mussi-Pinhata, MM; Peixoto, MF; Pilotto, JH; Read, J; Souza, Rda S; Stoszek, SK,
)
" M1 was found in only minor to moderate quantities in plasma from preclinical species dosed with GDC-0834."( Significant species difference in amide hydrolysis of GDC-0834, a novel potent and selective Bruton's tyrosine kinase inhibitor.
Baumgardner, M; Boggs, J; Coraggio, M; Currie, KS; Davis, JC; Deese, A; Gopaul, S; Halladay, JS; Hop, CE; Khojasteh, SC; Kuebler, P; La, H; Le, H; Liao, XC; Liu, L; Lubach, JW; Shin, Y; Sowell, CG; Wong, H; Wong, S; Young, WB, 2011
)
" Finally, AZD9668 prevented airspace enlargement and small airway wall remodeling in guinea pigs in response to chronic tobacco smoke exposure whether dosed therapeutically or prophylactically."( AZD9668: pharmacological characterization of a novel oral inhibitor of neutrophil elastase.
Churg, A; Ekholm, K; Falk-Håkansson, H; Gränse, M; Jungar, C; Kozma, V; Lal, H; Lindahl, M; Ottosson, T; Sanfridson, A; Stevens, T; Wright, JL, 2011
)
" Dosed alone, compound 64 suppressed extinction of conditioned freezing (10 mg/kg) and rapid eye movement (REM) sleep (30 mg/kg), consistent with previous reports for rimonabant, although for REM sleep, compound 64 was greater than threefold less potent than for metabolic effects."( Characterization of a novel, brain-penetrating CB1 receptor inverse agonist: metabolic profile in diet-induced obese models and aspects of central activity.
Chaperon, F; Chen, YA; Commerford, SR; Dardik, B; Gerber, SP; Gromada, J; He, X; Hollenbeck, T; Jacobson, LH; Jaton, AL; Liu, H; McNamara, P; Nguyen-Tran, V; Schwartzkopf, C; Seidel, HM; Teixeira, S, 2011
)
"Polymeric quick-dissolving films were developed as a solid dosage topical microbicide formulation for the vaginal delivery of the highly potent and non-toxic, dual-acting HIV nonnucleoside reverse transcriptase inhibitor (NNRTI) pyrimidinedione, IQP-0528."( Vaginal film drug delivery of the pyrimidinedione IQP-0528 for the prevention of HIV infection.
Boczar, A; Buckheit, RW; Ham, AS; Rohan, LC; W Buckheit, K; Yang, L, 2012
)
"Based on the above evaluations, a vaginal film formulation has been identified as a potential solid dosage form for the vaginal delivery of the topical microbicide candidate IQP-0528."( Vaginal film drug delivery of the pyrimidinedione IQP-0528 for the prevention of HIV infection.
Boczar, A; Buckheit, RW; Ham, AS; Rohan, LC; W Buckheit, K; Yang, L, 2012
)
" Compounds were dosed 30 min before the learning trial of the task."( Phosphodiesterase type 5 (PDE5) inhibition improves object recognition memory: indications for central and peripheral mechanisms.
Akkerman, S; Blokland, A; Menniti, FS; Prickaerts, J; Reneerkens, OA; Rutten, K; Shaffer, CL; Steinbusch, HW, 2012
)
" Intermittent and continuous dosing regimens were analysed."( Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial.
Becerra, C; Bendell, JC; Burris, HA; Cox, DS; DeMarini, DJ; Eckhardt, G; Falchook, GS; Fecher, LA; Flaherty, K; Gordon, MS; Hart, L; Infante, JR; Kurzrock, R; Le, NT; Messersmith, WA; Morris, SR; Nallapareddy, S; Peddareddigari, VG; Xu, Y, 2012
)
" Furthermore, mean concentrations in plasma were greater than the preclinical target concentration throughout the dosing interval."( Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial.
Becerra, C; Bendell, JC; Burris, HA; Cox, DS; DeMarini, DJ; Eckhardt, G; Falchook, GS; Fecher, LA; Flaherty, K; Gordon, MS; Hart, L; Infante, JR; Kurzrock, R; Le, NT; Messersmith, WA; Morris, SR; Nallapareddy, S; Peddareddigari, VG; Xu, Y, 2012
)
"The objective of this study was to compare the bioavailability and tolerability of revaprazan and itopride combination therapy to those of equally dosed monotherapies to acquire basic drug-drug interaction information about revaprazan."( Bioavailability and tolerability of combination treatment with revaprazan 200 mg + itopride 150 mg: a randomized crossover study in healthy male Korean volunteers.
Bae, KS; Choi, HY; Jang, SB; Jin, SJ; Kim, MJ; Kim, YH; Lee, SJ; Lim, HS; Noh, YH; Sung, H, 2012
)
"5mg) was escalated in a 3+3 design with standard gemcitabine dosing (1000 mg/m(2) IV Days 1, 8, and 15 of 28-day cycles)."( A phase 1b study of trametinib, an oral Mitogen-activated protein kinase kinase (MEK) inhibitor, in combination with gemcitabine in advanced solid tumours.
Bellew, KM; Bendell, JC; Burris, HA; Cox, DS; Durante, M; Infante, JR; Jones, SF; Le, NT; Papadopoulos, KP; Park, JJ; Patnaik, A; Rasco, D; Smith, L; Tolcher, AW, 2013
)
"Administration of trametinib at its full monotherapy dose of 2mg daily in combination with standard gemcitabine dosing (1000 mg/m(2) IV Days 1, 8, and 15 every 28 days) was feasible."( A phase 1b study of trametinib, an oral Mitogen-activated protein kinase kinase (MEK) inhibitor, in combination with gemcitabine in advanced solid tumours.
Bellew, KM; Bendell, JC; Burris, HA; Cox, DS; Durante, M; Infante, JR; Jones, SF; Le, NT; Papadopoulos, KP; Park, JJ; Patnaik, A; Rasco, D; Smith, L; Tolcher, AW, 2013
)
"The novel antibiotic MBX-500, dosed at 100, 200, or 400 mg/kg twice daily for 7 days, was evaluated for the treatment of Clostridium difficile infection (CDI) in the gnotobiotic pig model."( MBX-500 is effective for treatment of Clostridium difficile infection in gnotobiotic piglets.
Beamer, G; Bowlin, T; Butler, M; Steele, J; Tzipori, S; Zhang, Q, 2013
)
"We compared on-demand dosing of dapoxetine alone and combined with mirodenafil in subjects with lifelong PE and without erectile dysfunction (ED)."( Comparison between on-demand dosing of dapoxetine alone and dapoxetine plus mirodenafil in patients with lifelong premature ejaculation: prospective, randomized, double-blind, placebo-controlled, multicenter study.
Cho, JS; Cho, ST; Lee, SH; Lee, SK; Lee, WK; Lee, YS; Oh, CY; Yang, DY; Yoo, C, 2013
)
" Low adherence linked with frequent dosing and short therapeutic duration has emerged as the major reason for inconsistent efficacy outcomes with gels in clinical trials."( Osmotic pump tablets for delivery of antiretrovirals to the vaginal mucosa.
Herold, BC; Kiser, PF; Mesquita, PM; Rastogi, R; Teller, RS, 2013
)
" The continued MAPK signaling-based resistance identified in these patients suggests that alternative dosing of current agents, more potent RAF/MEK inhibitors, and/or inhibition of the downstream kinase ERK may be needed for durable control of BRAF-mutant melanoma."( MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition.
Anderka, K; Carter, SL; Cibulskis, K; Cooper, ZA; Farlow, DN; Fisher, S; Flaherty, KT; Frederick, DT; Friedrich, DC; Gabriel, SB; Garraway, LA; Getz, G; Goetz, EM; Hodis, E; Johannessen, CM; Kryukov, G; Lawrence, DP; McKenna, A; Perrin, D; Rosenberg, M; Sullivan, RJ; Taylor-Weiner, A; Treacy, DJ; Van Allen, EM; Wagle, N; Wargo, JA, 2014
)
" These eruptions seem to be reduced when dosed in combination with dabrafenib."( Acneiform eruptions: a common cutaneous toxicity of the MEK inhibitor trametinib.
Anforth, R; Clements, A; Fernandez-Peñas, P; Kefford, R; Liu, M; Long, GV; Nguyen, B; Uribe, P, 2014
)
" The primary endpoint of study 2 was maximum FEV1 reached during 6 h after dosing with RPL554 in patients with asthma."( Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials.
Banner, KH; Burggraaf, J; Calzetta, L; Cazzola, M; Cohen, AF; de Kam, ML; Diamant, Z; Franciosi, LG; Kamerling, IM; Morelli, N; Page, CP; Singh, D; Spina, D; Walker, MJ; Zuiker, R, 2013
)
" Patients were assigned to one of 10 different cohorts, involving either daily dosing with both agents or daily dosing with trametinib and intermittent everolimus dosing."( A phase IB trial of the oral MEK inhibitor trametinib (GSK1120212) in combination with everolimus in patients with advanced solid tumors.
Bellew, KM; Bendell, JC; Burris, HA; Cox, DS; Durante, M; Infante, JR; Jones, SF; Le, NT; Papadopoulos, KP; Park, J; Patnaik, A; Rasco, D; Tolcher, AW, 2015
)
" In vivo murine modeling with eleven patient-derived melanoma explants evaluated daily dosing of TAK-733 at 25 or 10 mg/kg."( Antitumor activity of the MEK inhibitor TAK-733 against melanoma cell lines and patient-derived tumor explants.
Brunkow, KL; Davis, SL; Eckhardt, SG; Fabrey, R; Gangolli, E; Klauck, PJ; Micel, LN; O'Connell, SM; Pitts, TM; Robertson, KM; Selby, HM; Tan, AC; Tentler, JJ; Vincent, PW, 2015
)
" Intermittent dosing schedule [1."( Phase I study of the MEK inhibitor trametinib in combination with the AKT inhibitor afuresertib in patients with solid tumors and multiple myeloma.
Aktan, G; Allred, AJ; Becerra, CR; Cornfeld, M; Ferron-Brady, G; Gauvin, J; Ibrahim, N; Motwani, M; Orford, K; Papadopoulos, KP; Patnaik, A; Rasco, DW; Tolcher, AW, 2015
)
"Continuous daily dosing of trametinib/afuresertib combination was poorly tolerated."( Phase I study of the MEK inhibitor trametinib in combination with the AKT inhibitor afuresertib in patients with solid tumors and multiple myeloma.
Aktan, G; Allred, AJ; Becerra, CR; Cornfeld, M; Ferron-Brady, G; Gauvin, J; Ibrahim, N; Motwani, M; Orford, K; Papadopoulos, KP; Patnaik, A; Rasco, DW; Tolcher, AW, 2015
)
"Developing new antiretroviral therapies for HIV-1 infection with potential for less frequent dosing represents an important goal within drug discovery."( Discovery of MK-8970: an acetal carbonate prodrug of raltegravir with enhanced colonic absorption.
Balsells, J; Bennet, A; Bennett, DJ; Ceglia, SS; Chessen, G; Clas, SD; Coleman, PJ; Dang, Q; de Lera Ruiz, M; Di Marco, CN; Grobler, J; Hafey, M; Higgins, J; John, C; Kim, SH; Li, J; Manser, K; Nissley, B; Nofsinger, R; Sanchez, RI; Sanders, JM; Smith, R; Templeton, A; Wai, JS; Walji, AM; Wang, J; Wu, Y, 2015
)
" The recommended dosage of trametinib monotherapy is 2 mg orally once daily until disease progression or unacceptable toxicity occurs."( Trametinib: a novel signal transduction inhibitor for the treatment of metastatic cutaneous melanoma.
Chung, C; Reilly, S, 2015
)
" Tumours showed a reduced growth in response to the MEK inhibitors, but halting the selumetinib dosing resulted in tumour relapse."( Antitumour efficacy of the selumetinib and trametinib MEK inhibitors in a combined human airway-tumour-stroma lung cancer model.
Boda, B; CaulFuty, M; Constant, S; Huang, S; Mas, C; Wiszniewski, L, 2015
)
"TAK-733 was administered orally by gavage to nude xenograft rats for 2 weeks, at dosage levels of 0 (0."( Evaluation of the therapeutic efficacy of a MEK inhibitor (TAK-733) using ¹⁸F-fluorodeoxyglucose-positron emission tomography in the human lung xenograft model A549.
Ishino, S; Miyake, H; Mori, I; Vincent, P, 2015
)
" Maize exhibits relative tolerance against compound 9F-6 at the dosage of 150 g ai/ha, but it is susceptible to saflufenacil even at 75 g ai/ha."( Synthesis, Herbicidal Activity, and QSAR of Novel N-Benzothiazolyl- pyrimidine-2,4-diones as Protoporphyrinogen Oxidase Inhibitors.
Niu, CW; Su, SW; Wu, Q; Xi, Z; Yang, GF; Zuo, Y, 2016
)
" The potent cytotoxicity of AZD1775, unrelated to WEE1 inhibition, may result in dose-limiting toxicities and exacerbate adverse effects; therefore, WEE1 inhibitors that demonstrate low cytotoxicity could be dosed at higher concentrations to chemosensitize the tumor and potentiate the effect of DNA-damaging agents such as cisplatin."( A WEE1 Inhibitor Analog of AZD1775 Maintains Synergy with Cisplatin and Demonstrates Reduced Single-Agent Cytotoxicity in Medulloblastoma Cells.
Amani, V; Backos, DS; Donson, AM; Foreman, NK; Harris, PS; Matheson, CJ; Reigan, P; Venkataraman, S; Vibhakar, R; Wempe, MF, 2016
)
"No dosage adjustments are required with any of the covariates tested."( Population pharmacokinetics and exposure-response of trametinib, a MEK inhibitor, in patients with BRAF V600 mutation-positive melanoma.
Chiu, J; Cox, D; Crist, W; DeMarini, DJ; Gardner, O; Kassir, N; Leonowens, C; Mouksassi, MS; Ouellet, D; Patel, K, 2016
)
" In a screen of 22,737 experiments of 583 doublet combinations in 39 diverse cancer cell lines using a 4 by 4 dosing regimen, both well-known and novel synergistic and efficacious combinations were identified."( An Unbiased Oncology Compound Screen to Identify Novel Combination Strategies.
Arthur, W; Benita, Y; Bloecher, A; Chenard, M; Cristescu, R; Feldman, I; Haines, BB; Kral, A; Lejnine, S; Li, J; Liu, Y; Loboda, A; O'Neil, J; Roberts, B; Shumway, SD; Winter, C; Zhang, T, 2016
)
" In 16 patients the first plasma sample was obtained before the first dosing of dabrafenib/trametinib."( Quantitative assessment of BRAF V600 mutant circulating cell-free tumor DNA as a tool for therapeutic monitoring in metastatic melanoma patients treated with BRAF/MEK inhibitors.
Bott, A; Buyl, R; Chevolet, I; Jacobs, B; Jansen, Y; Maertens, G; Meersseman, G; Neyns, B; Schreuer, M; Seremet, T; Van Den Herrewegen, S; Wilgenhof, S, 2016
)
" Although previous studies have shown synergistic activity when pan-PI3K inhibitors were combined with MAPK inhibitors in the treatment of melanoma exhibiting concurrent genetic abnormalities, overlapping adverse events in patients limit optimal dosing and clinical application."( Concomitant Inhibition of PI3Kβ and BRAF or MEK in PTEN-Deficient/BRAF-Mutant Melanoma Treatment: Preclinical Assessment of SAR260301 Oral PI3Kβ-Selective Inhibitor.
Bonnevaux, H; Delorme, C; Garcia-Echeverria, C; Halley, F; Lemaitre, O; Lengauer, C; Levit, MN; Vincent, L; Virone-Oddos, A; Windenberger, F, 2016
)
"Eligible patients with solid tumours received placebo on day 1, once-daily trametinib 2-mg doses on days 2-14, and a single trametinib 3-mg dose on day 15 to achieve supratherapeutic dosing for QTc measurement."( Phase 1 study to evaluate the effect of the MEK inhibitor trametinib on cardiac repolarization in patients with solid tumours.
Bauman, JW; Beeram, M; Cox, DS; Hamid, M; Papadopoulos, KP; Patel, BR; Patnaik, A; Rasco, D; Scheuber, A; Schramek, D; Sharma, S; Tolcher, A; Werner, TL; Zhou, Y, 2016
)
" When dosed orally in mice at 50mg/kg twice a day (BID), 48 showed an unbound maximal plasma concentration (Cmax) >15-fold over its cell EC50, thereby providing a robust chemical probe for studying KDM5 biological functions in vivo."( Lead optimization of a pyrazolo[1,5-a]pyrimidin-7(4H)-one scaffold to identify potent, selective and orally bioavailable KDM5 inhibitors suitable for in vivo biological studies.
Classon, M; Cummings, R; Deshmukh, G; Dragovich, PS; Gehling, VS; Gustafson, A; Harmange, JC; Kiefer, JR; Labadie, S; Lai, T; Liang, J; Liao, J; Liederer, BM; Liu, Y; Mao, W; Murray, L; Ortwine, DF; Trojer, P; Van der Porten, E; Vinogradova, M; Zhang, B; Zheng, X, 2016
)
" Results 57 patients were enrolled onto the continuous dosing cohort and 12 patients onto an intermittent BID dosing cohort."( A phase Ib dose-escalation study of the MEK inhibitor trametinib in combination with the PI3K/mTOR inhibitor GSK2126458 in patients with advanced solid tumors.
Bedard, PL; Bendell, J; Burris, HA; Cartee, L; Cornfeld, M; Del Conte, G; Fasolo, A; Greenwood, R; Grilley-Olson, JE; Infante, JR; Lee, CB; Razak, AR; Sessa, C; Singh, R; Stayner, LA; Wu, Y, 2016
)
" The same dosing regimen of topical BRAF inhibitor does not increase the incidence of cutaneous squamous cell carcinomas in mice."( Cutaneous wound healing through paradoxical MAPK activation by BRAF inhibitors.
Atefi, M; Azhdam, A; Cochran, AJ; Comin-Anduix, B; de-Faria, FM; Escuin-Ordinas, H; Herschman, HR; Huang, RR; Hugo, W; Jiao, J; Komenan, SM; Krystofinski, P; Li, S; Lo, RS; McBride, WH; Modlin, RL; Pellegrini, M; Realegeno, S; Ribas, A; Segura, T; Sun, L; Xie, MW, 2016
)
"A multi-institutional, randomized phase II trial of continuous dosing of dabrafenib with or without trametinib is ongoing in metastatic thyroid cancer."( Intermittent Dosing of Dabrafenib and Trametinib in Metastatic BRAF
Eton, O; Lee, SL; Pudusseri, A; White, PS, 2017
)
" They also noted improved tolerance of treatment upon transitioning to the intermittent dosing schedule."( Intermittent Dosing of Dabrafenib and Trametinib in Metastatic BRAF
Eton, O; Lee, SL; Pudusseri, A; White, PS, 2017
)
" The challenges ahead are in the establishment of the optimum dosing schedule either alone or in combination and the identification of patients with specific biomarker profiles who benefit most."( Strategic development of AZD1775, a Wee1 kinase inhibitor, for cancer therapy.
Fu, S; Keyomarsi, K; Meric-Bernstein, F; Wang, Y, 2018
)
" In addition, the pulsatile dosing schedule alone shows superior anti-tumor effects and delays the emergence of drug resistance."( Pulsatile MEK Inhibition Improves Anti-tumor Immunity and T Cell Function in Murine Kras Mutant Lung Cancer.
Akbay, EA; Boiarsky, J; Brea, EJ; Choi, H; Deng, J; Dong, L; Houghton, S; Li, S; Merghoub, T; Redmond, D; Silk, T; Smith, PD; Wolchok, JD; Wong, KK; Zhong, H, 2019
)
"This study aimed to investigate the dose-response and pharmacology of a range of single doses of nebulised ensifentrine (RPL554), an inhaled dual phosphodiesterase (PDE) 3/4 inhibitor in patients with asthma."( Efficacy and safety of a first-in-class inhaled PDE3/4 inhibitor (ensifentrine) vs salbutamol in asthma.
Abbott-Banner, K; Bjermer, L; Newman, K, 2019
)
" For the two co-primary endpoints there was a clear ensifentrine dose-response relationship, with all treatments superior to placebo (p < 0."( Efficacy and safety of a first-in-class inhaled PDE3/4 inhibitor (ensifentrine) vs salbutamol in asthma.
Abbott-Banner, K; Bjermer, L; Newman, K, 2019
)
" Among 126 enrolled patients, 63 received continuous oral daily dosing of trametinib and uprosertib, 29 received various alternative dosing schedules, and 34 were enrolled into expansion cohorts."( Phase I dose-escalation trial of the oral AKT inhibitor uprosertib in combination with the oral MEK1/MEK2 inhibitor trametinib in patients with solid tumors.
Becerra, C; D'Amelio, AM; Ellis, C; Gauvin, J; Gonzalez, R; Heist, RS; Ibrahim, N; Kalyana-Sundaram, S; Kleha, JF; Kurzrock, R; Leonowens, C; Means-Powell, J; Tan, AR; Tolcher, AW; Valero, V; Wang, C; Werner, TL; Yan, L, 2020
)
"Continuous and intermittent dosing of trametinib in combination with uprosertib was not tolerated, and minimal clinical activity was observed in all schedules tested."( Phase I dose-escalation trial of the oral AKT inhibitor uprosertib in combination with the oral MEK1/MEK2 inhibitor trametinib in patients with solid tumors.
Becerra, C; D'Amelio, AM; Ellis, C; Gauvin, J; Gonzalez, R; Heist, RS; Ibrahim, N; Kalyana-Sundaram, S; Kleha, JF; Kurzrock, R; Leonowens, C; Means-Powell, J; Tan, AR; Tolcher, AW; Valero, V; Wang, C; Werner, TL; Yan, L, 2020
)
"Lapatinib and trametinib could be combined in an intermittent dosing schedule in patients with manageable toxicity."( Phase I study of lapatinib plus trametinib in patients with KRAS-mutant colorectal, non-small cell lung, and pancreatic cancer.
Beijnen, JH; Bernards, R; Huijberts, SCFA; Huitema, ADR; Marchetti, S; Monkhorst, K; Opdam, FL; Pulleman, S; Rosing, H; Schellens, JHM; Steeghs, N; Thijssen, B; van Brummelen, EMJ; van Geel, RMJM, 2020
)
"To support future dosing recommendations, the effect of food on the pharmacokinetics of adavosertib, a first-in-class, small-molecule reversible inhibitor of WEE1 kinase, was assessed in patients with advanced solid tumors."( Effect of food on the pharmacokinetics of the WEE1 inhibitor adavosertib (AZD1775) in patients with advanced solid tumors.
Ah-See, ML; Campone, M; Labots, M; Li, Y; Mugundu, G; Någård, M; Ottesen, L; Ravaud, A; Roxburgh, P; So, K; Thistlethwaite, F; Valkenburg-van Iersel, L; Vermunt, M, 2020
)
"0% of patients in the AZD2811NP arm using the current dosing schedule."( Biomarker-driven phase 2 umbrella trial study for patients with recurrent small cell lung cancer failing platinum-based chemotherapy.
Ahn, JS; Ahn, MJ; Godin, RE; Hollingsworth, SJ; Jung, HA; Kim, HJ; Lee, SH; Mortimer, PGS; Park, K; Park, S; Park, WY; Shim, J; Smith, SA; Sun, JM, 2020
)
" The effects of AZD3965 on visual acuity and electroretinography (ERG) were further investigated in pigmented (Long-Evans) rats, with dosing for up to 7 days."( Effects of a monocarboxylate transport 1 inhibitor, AZD3965, on retinal and visual function in the rat.
Allen, AE; Grant, C; Greenwood, K; Lucas, RJ; Martin, EA; Redfern, WS; Vince, P, 2020
)
" The major adverse events with relugolix were hot flush, metrorrhagia, menorrhagia, and irregular menstruation, and bone mineral density decrease in a dose-response manner, which were also observed in the leuprorelin group with a frequency comparable with that in the relugolix 40-mg group."( Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosis-associated pain in a dose-response manner: a randomized, double-blind, placebo-controlled study.
Kudou, K; Kusumoto, T; Osuga, Y; Seki, Y; Tanimoto, M; Terakawa, N, 2021
)
"Oral administration of relugolix alleviated endometriosis-associated pain in a dose-response manner and was generally well tolerated."( Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosis-associated pain in a dose-response manner: a randomized, double-blind, placebo-controlled study.
Kudou, K; Kusumoto, T; Osuga, Y; Seki, Y; Tanimoto, M; Terakawa, N, 2021
)
" On cycle 1 day 8 (pre-dose), tumor pY15-Cdk levels were higher than baseline in four of eight patients, suggesting target rebound during the day 5 to 8 dosing break."( Safety, Antitumor Activity, and Biomarker Analysis in a Phase I Trial of the Once-daily Wee1 Inhibitor Adavosertib (AZD1775) in Patients with Advanced Solid Tumors.
Bruns, A; Chang, TC; Chen, AP; Chen, L; Das, B; Do, K; Doroshow, JH; Ji, J; Juwara, L; Kinders, RJ; Kummar, S; Miller, SB; Mittra, A; Mugundu, G; Naqash, AR; O'Sullivan Coyne, G; Parchment, RE; Piekarz, R; Rubinstein, L; Sharon, E; Streicher, H; Takebe, N; Wilsker, D; Zlott, J, 2021
)
"Relugolix decreased menstrual blood loss in women with uterine leiomyomas in a dose-response manner, and was generally well tolerated."( Relugolix for oral treatment of uterine leiomyomas: a dose-finding, randomized, controlled trial.
Hoshiai, H; Kudou, K; Kusumoto, T; Seki, Y; Tanimoto, M, 2021
)
"Eligible participants will receive adavosertib monotherapy until disease progression or unacceptable toxicity, starting at the recommended phase II dosing of adavosertib 300 mg daily days 1 through 5 and 8 through 12 of a 21-day cycle."( ADAGIO: a phase IIb international study of the Wee1 inhibitor adavosertib in women with recurrent or persistent uterine serous carcinoma.
Colombo, N; Liu, J; Oaknin, A; Oza, AM, 2022
)
"Patients received intermittent or concurrent dosing of pembrolizumab plus trametinib."( KEYNOTE-022: Pembrolizumab with trametinib in patients with BRAF wild-type melanoma or advanced solid tumours irrespective of BRAF mutation.
Ascierto, PA; Butler, MO; Carlino, MS; Croydon, E; Del Vecchio, M; Diede, SJ; Ferrucci, PF; Gasal, E; Ghori, R; Hamid, O; Joshua, AM; Maio, M; McWhirter, E; Miller, WH; Ribas, A; Zielinski, RR, 2022
)
"MTDs for concurrent and intermittent dosing of pembrolizumab with trametinib were identified."( KEYNOTE-022: Pembrolizumab with trametinib in patients with BRAF wild-type melanoma or advanced solid tumours irrespective of BRAF mutation.
Ascierto, PA; Butler, MO; Carlino, MS; Croydon, E; Del Vecchio, M; Diede, SJ; Ferrucci, PF; Gasal, E; Ghori, R; Hamid, O; Joshua, AM; Maio, M; McWhirter, E; Miller, WH; Ribas, A; Zielinski, RR, 2022
)
" Previous preclinical studies suggested that an intermittent dosing of these drugs could delay the emergence of resistance."( Intermittent BRAF inhibition in advanced BRAF mutated melanoma results of a phase II randomized trial.
Arance, A; Basterretxea, L; Bellido, L; Berciano-Guerrero, MA; Berrocal, A; Campos, B; Cerezuela, P; de la Cruz, L; Diaz Beveridge, R; Drozdowskyj, A; Espinosa, E; Gonzalez-Cao, M; Lopez-Martin, JA; Mayo de Las Casas, C; Molina, MA; Montagut, C; Muñoz-Couselo, E; Ochenduszko, S; Oramas, J; Puertolas, T; Rodriguez, D; Villanueva, MJ, 2021
)
" A monitoring protocol was established to standardize medication dosing and monitoring of outcome measures."( Trametinib for Refractory Chylous Effusions and Systemic Complications in Children with Noonan Syndrome.
Annam, A; Chatfield, KC; Hill, LR; Kulungowski, AM; McCallen, LM; Nakano, TA; Rankin, AW, 2022
)
" Dosing adherence to a daily tablet may also be an issue in comparison to injections at 3-mo intervals."( Relugolix: Five Reasons Why the US Food and Drug Administration Should Have Exercised Restraint.
Burns, MC; Powell, K; Prasad, V, 2023
)
" This study investigated dosing schedules for adavosertib monotherapy, determining the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) in patients with advanced solid tumors."( A phase Ib study of adavosertib, a selective Wee1 inhibitor, in patients with locally advanced or metastatic solid tumors.
Chmielecki, J; Falchook, GS; Imedio, ER; Jenkins, S; Johnson, M; Jones, S; Kumar, S; Mugundu, GM; Sachdev, J; Spigel, DR, 2023
)
" The combination of magnetically controlled drug delivery and supramolecular engineering can help to reduce the dosage of AMPs, control the delivery, and improve their cytocompatibility."( Iron Oxide Nanoparticles with Supramolecular Ureido-Pyrimidinone Coating for Antimicrobial Peptide Delivery.
Bellan, R; Berensmeier, S; Cookman, J; Dankers, PYW; Paar, M; Schwaminger, SP; Song, J; Turrina, C, 2023
)
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (5,841)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990612 (10.48)18.7374
1990's533 (9.13)18.2507
2000's1723 (29.50)29.6817
2010's2266 (38.79)24.3611
2020's707 (12.10)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials604 (9.97%)5.53%
Reviews340 (5.61%)6.00%
Case Studies347 (5.73%)4.05%
Observational11 (0.18%)0.25%
Other4,757 (78.51%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]