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fosphenytoin

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Description

fosphenytoin: structure given in first & second source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID56339
CHEMBL ID1201336
CHEBI ID5165
SCHEMBL ID94254
MeSH IDM0127036

Synonyms (45)

Synonym
BIDD:GT0220
93390-81-9
fosphenytoin
C07840
np-06
DB01320
(3-phosphoryloxymethyl)phenytoin
fosphenytoine [inn-french]
fosphenytoinum [inn-latin]
2,4-imidazolidinedione, 5,5-diphenyl-3-((phosphonooxy)methyl)-, (sp-4-2)-
fosfenitoina [inn-spanish]
2,4-imidazolidinedione, 5,5-diphenyl-3-((phosphonooxy)methyl)-
fosphenytoin [inn:ban]
D07993
fosphenytoin (inn)
(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)methyl dihydrogen phosphate
CHEMBL1201336
chebi:5165 ,
hsdb 7523
unii-b4sf212641
b4sf212641 ,
fosphenytoine
fosfenitoina
fosphenytoinum
fosphenytoin [mi]
fosphenytoin [hsdb]
3-(hydroxymethyl)-5,5-diphenylhydantoin, phosphate (ester)
fosphenytoin [who-dd]
fosphenytoin [vandf]
fosphenytoin [inn]
[(2-hydroxy-5-oxo-4,4-diphenyl-4,5-dihydro-1h-imidazol-1-yl)methoxy]phosphonic acid
gtpl7190
SCHEMBL94254
dtxsid9044299 ,
cas-93390-81-9
NCGC00249894-01
tox21_113670
dtxcid7024299
[(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)methoxy]phosphonic acid
XWLUWCNOOVRFPX-UHFFFAOYSA-N
Q5473363
FT-0738599
EN300-18563827
CS-0013613
HY-B1657

Research Excerpts

Overview

Fosphenytoin (Cerebyx), is a water soluble prodrug that is rapidly and completely converted to phenytoin. It is a phosphate ester prodrug developed as a replacement for standard injectable sodium pheny Toin. FosphenyToin is a new anti-seizure drug.

ExcerptReferenceRelevance
"Fosphenytoin is a phosphate ester prodrug developed as an alternative to intravenous phenytoin for acute treatment of seizures. "( Fosphenytoin: clinical pharmacokinetics and comparative advantages in the acute treatment of seizures.
Fischer, JH; Fischer, PA; Patel, TV, 2003
)
3.2
"Fosphenytoin is a water-soluble disodium phosphate ester of phenytoin that is converted in plasma to phenytoin. "( Intravenous administration of fosphenytoin: options for the management of seizures.
DeToledo, J; Ramsay, RE, 1996
)
2.03
"Fosphenytoin is a new phenytoin prodrug that fulfills many of the properties of an ideal anticonvulsant drug."( Intramuscular use of fosphenytoin: an overview.
Ramsay, RE; Uthman, BM; Wilder, BJ, 1996
)
1.33
"Fosphenytoin is a phenytoin prodrug that received an approvable letter from the Food and Drug Administration in February 1996. "( Fosphenytoin: a novel phenytoin prodrug.
Boucher, BA,
)
3.02
"Fosphenytoin is a phosphate ester prodrug of phenytoin developed as a replacement for standard injectable sodium phenytoin. "( Fosphenytoin (Cerebyx).
Browne, TR, 1997
)
3.18
"Fosphenytoin (Cerebyx), is a water soluble prodrug that is rapidly and completely converted to phenytoin. "( Intramuscular fosphenytoin (Cerebyx) in patients requiring a loading dose of phenytoin.
Barkley, GL; Garnett, WR; Knapp, LE; Leppik, IE; Pellock, JM; Ramsay, RE; Uthman, BM; Wilder, BJ, 1997
)
2.1
"Fosphenytoin is a parenteral prodrug of phenytoin that is more tolerable than parenteral phenytoin."( Newer antiepileptic drugs: gabapentin, lamotrigine, felbamate, topiramate and fosphenytoin.
Curry, WJ; Kulling, DL, 1998
)
1.25
"Fosphenytoin is a phenytoin prodrug that has been introduced to overcome some of the problems and limitations associated with parenteral phenytoin sodium administration. "( Fosphenytoin.
Luer, MS, 1998
)
3.19
"Fosphenytoin is a new phosphate ester prodrug of phenytoin. "( Elevated free fosphenytoin concentrations in uremic sera: uremic toxins hippuric acid and indoxyl sulfate do not account for the impaired protein binding of fosphenytoin.
Dasgupta, A; Havlik, D, 1998
)
2.1
"Fosphenytoin is a parenterally administered prodrug of phenytoin, used in the treatment of patients with seizures."( Fosphenytoin. Pharmacoeconomic implications of therapy.
Benfield, P; Holliday, SM; Plosker, GL, 1998
)
2.46
"Fosphenytoin is a phosphate ester prodrug of phenytoin that is significantly better tolerated parenterally than phenytoin in the treatment of epilepsy."( Fosphenytoin: an intravenous option for the management of acute trigeminal neuralgia crisis.
Cheshire, WP, 2001
)
2.47
"Fosphenytoin is a prodrug that is metabolized by phosphatases to yield the antiepileptic drug phenytoin plus inorganic phosphate. "( Hypocalcemia-like electrocardiographic changes after administration of intravenous fosphenytoin.
Blackshear, JL; Bondy, LR; Keegan, MT; Lanier, WL, 2002
)
1.98

Effects

Fosphenytoin has advantages over phenytoin injection that are related to its greater aqueous solubility. It obviates the extreme alkalinity, propylene glycol, and ethanol needed in the injectable pheny Toin formulation. FosphenyToin has been tested successfully for three indications in humans.

ExcerptReferenceRelevance
"Fosphenytoin has fewer local adverse effects (e.g., pain, burning, and itching at the injection site) after i.m."( Pharmacology and pharmacokinetics of fosphenytoin.
Browne, TR; Eldon, MA; Kugler, AR, 1996
)
1.29
"Fosphenytoin has advantages over phenytoin injection that are related to its greater aqueous solubility, which obviates the extreme alkalinity, propylene glycol, and ethanol needed in the injectable phenytoin formulation."( Safety of fosphenytoin sodium.
Benezra, DA; Fierro, LS; Savulich, DH, 1996
)
1.42
"Fosphenytoin has been tested successfully for three indications in humans: intramuscular maintenance dosing, intramuscular loading dose administration, and intravenous treatment of status epilepticus."( Fosphenytoin (Cerebyx).
Browne, TR, 1997
)
2.46
"Fosphenytoin has recently been approved as a substitute for parenteral phenytoin."( New drug therapy for acute seizure management.
Morton, LD; Pellock, JM; Rizkallah, E, 1997
)
1.02
"Fosphenytoin has several advantages and disadvantages that should be considered when selecting its use in place of parenteral phenytoin."( Fosphenytoin.
Luer, MS, 1998
)
2.46

Treatment

ExcerptReferenceRelevance
"With fosphenytoin treatment 5 min after ischemia, hippocampal CA1 pyramidal neurons remained at near control level (13.90 +/- 0.92), however, GFAP staining was not significantly changed."( Fosphenytoin reduces hippocampal neuronal damage in rat following transient global ischemia.
Chan, SA; Iyer, V; Miller, JJ; Reid, KH; Schurr, A; Tseng, MT, 1998
)
2.2

Toxicity

Intravenous fosphenytoin has been associated with less soft-tissue injury and fewer adverse effects in general than phenytoin. Adverse events associated with fosp Pittsburghtoin generally were related to the central nervous system and were similar to those associated with pheny Toin.

ExcerptReferenceRelevance
"Both groups had similar types and frequencies of mild to moderate adverse events."( Safety and tolerance of multiple doses of intramuscular fosphenytoin substituted for oral phenytoin in epilepsy or neurosurgery.
Campbell, K; Garnett, WR; Henkin, SA; Kugler, AR; Pellock, JM; Ramsay, RE; Wilder, BJ, 1996
)
0.54
" Intramuscular fosphenytoin is a safe and well-tolerated alternative to oral phenytoin when oral administration is not feasible."( Safety and tolerance of multiple doses of intramuscular fosphenytoin substituted for oral phenytoin in epilepsy or neurosurgery.
Campbell, K; Garnett, WR; Henkin, SA; Kugler, AR; Pellock, JM; Ramsay, RE; Wilder, BJ, 1996
)
0.89
"Intramuscular fosphenytoin was safe and well tolerated, with no irritation found for 99% of all injection site evaluations."( The safety, tolerability, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients.
Boucher, BA; Dean, JC; Feler, CA; Kramer, RE; Kugler, AR; Michie, DD; Parks, BR; Smith, KR; Tipton, BK; Young, B,
)
0.75
" Both routes are safe and well tolerated."( The safety, tolerability, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients.
Boucher, BA; Dean, JC; Feler, CA; Kramer, RE; Kugler, AR; Michie, DD; Parks, BR; Smith, KR; Tipton, BK; Young, B,
)
0.38
" Intravenous fosphenytoin has been associated with less soft-tissue injury and fewer adverse effects in general than phenytoin."( Safety of fosphenytoin sodium.
Benezra, DA; Fierro, LS; Savulich, DH, 1996
)
1.07
" Adverse events associated with fosphenytoin generally were related to the central nervous system and were similar to those associated with phenytoin, except for a higher incidence of transient pruritus with fosphenytoin."( Clinical experience with fosphenytoin in adults: pharmacokinetics, safety, and efficacy.
Knapp, LE; Kugler, AR, 1998
)
0.89
" We evaluated adverse events and length-of-stay using parenteral the two drugs in routine emergency department use."( Randomized evaluation of adverse events and length-of-stay with routine emergency department use of phenytoin or fosphenytoin.
Clements, EA; Cochran, MS; Coplin, WM; O'Neil, BJ; Rebuck, JA; Rhoney, DH, 2002
)
0.53
"5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects."( Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
Benz, RD; Contrera, JF; Kruhlak, NL; Matthews, EJ; Weaver, JL, 2004
)
0.32
" One patient experienced apnea and oral dyskinesia as adverse effects of fPHT, whereas arrhythmia, hypotension, obvious reduction of consciousness, local irritation, phlebitis and purple grove syndrome were not observed in any patient."( Efficacy and safety of fosphenytoin for acute encephalopathy in children.
Akasaka, M; Hasegawa, T; Ishidou, Y; Kikuchi, K; Nakazawa, M; Niijima, S; Okumura, A; Shima, T; Shimizu, T; Suzuki, T; Takanashi, J; Yamamoto, A, 2015
)
0.73
" Adverse effects of fosphenytoin, excessive sedation, or intravenous fluid incompatibility were not observed in any patients."( Efficacy and safety of fosphenytoin for benign convulsions with mild gastroenteritis.
Abe, S; Igarashi, A; Ikeno, M; Nakahara, E; Nakazawa, M; Niijima, S; Okumura, A; Shimizu, T; Toda, S; Yamashita, S, 2015
)
1.05
" Adverse effects of fosphenytoin may include: cardiovascular events (hypotension, arrhythmias), paresthesias or pruritus or some central events - somnolence, headache, dizziness, nystagmus and ataxia."( The safety and efficacy of fosphenytoin for the treatment of status epilepticus.
Borowicz, KK; Czuczwar, SJ; Popławska, M, 2015
)
1.04
" Serum concentrations of free phenytoin were determined, and adverse events were assessed at 0, 10, 20 minutes, and 24 hours after the infusion of fosphenytoin."( Safety, Tolerability, and Pharmacokinetics of Fosphenytoin Loading in Patients With Subarachnoid Hemorrhage.
Chun, YI; Ji, M; Kim, DW; Kim, TE,
)
0.59
"Four patients experienced transient lowering of blood pressure, but other adverse events were not observed."( Safety, Tolerability, and Pharmacokinetics of Fosphenytoin Loading in Patients With Subarachnoid Hemorrhage.
Chun, YI; Ji, M; Kim, DW; Kim, TE,
)
0.39

Pharmacokinetics

Fosphenytoin is a water-soluble prodrug of phenytoin (PHT) Half-life for conversion of FOS to PHT ranges from 7-15 minutes. Study was performed to investigate the safety, tolerability, and pharmacokinetic profiles of rapid intravenous loading of fosphenyToin.

ExcerptReferenceRelevance
" No significant differences were observed in the fraction unbound or pharmacokinetic parameters of ACC-9653, phenytoin, or diazepam when ACC-9653 was administered alone compared to concomitant administration with diazepam."( Evaluation of the pharmacokinetic interaction between diazepam and ACC-9653 (a phenytoin prodrug) in healthy male volunteers.
Brouwer, KL; Donn, KH; Dukes, GE; Hak, LJ; Hussey, EK; Krol, TF; Messenheimer, JA, 1990
)
0.28
" The purpose of this study was to evaluate the pharmacokinetic profile of 1 following iv and im administration in adult patients receiving chronic oral phenytoin monotherapy."( Phenytoin prodrug 3-phosphoryloxymethyl phenytoin (ACC-9653): pharmacokinetics in patients following intravenous and intramuscular administration.
Achari, R; Bombassaro, AM; Boucher, BA; Rasmussen, SN; Turlapaty, P; Watridge, CB, 1989
)
0.28
" The prodrug, after achieving a maximum concentration at the end of the 30-minute infusion (Cmax 20, 36, 75, 129 micrograms/mL) declined rapidly with a half-life (t1/2) of about 8 minutes."( Safety, tolerance and pharmacokinetics of intravenous doses of the phosphate ester of 3-hydroxymethyl-5,5-diphenylhydantoin: a new prodrug of phenytoin.
Donn, KH; Gerber, N; Guthrie, RM; Laddu, A; Mays, DC; Quon, CY; Rivenburg, WK; Turlapaty, P, 1988
)
0.27
"Measurement of the absolute bioavailability of phenytoin (PHT) derived from test doses of phenytoin prodrug (PPD) at therapeutic PHT serum concentrations is complicated by two problems: 1) the area under the serum concentration versus time curve (AUC) produced by a given size of test dose will vary directly with background PHT serum concentration due to the nonlinear pharmacokinetic properties of PHT; 2) PPD is more water soluble than PHT, making renal excretion of PPD more likely."( Bioavailability studies of drugs with nonlinear pharmacokinetics: II. Absolute bioavailability of intravenous phenytoin prodrug at therapeutic phenytoin serum concentrations determined by double-stable isotope technique.
Browne, TR; Davoudi, H; Dougherty, CL; Evans, BA; Evans, JE; Kres, J; McEntegart, C; Miceli, JJ; Quon, C; Szabo, GK, 1993
)
0.29
"To evaluate the safety, tolerability, and pharmacokinetic profile of fosphenytoin, a water-soluble phenytoin prodrug, after intramuscular and intravenous administration."( The safety, tolerability, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients.
Boucher, BA; Dean, JC; Feler, CA; Kramer, RE; Kugler, AR; Michie, DD; Parks, BR; Smith, KR; Tipton, BK; Young, B,
)
0.62
"Stable isotope analogues of phenytoin are useful for pulse dose pharmacokinetic studies in epilepsy patients."( A capillary GC-MS method for analysis of phenytoin and [13C3]-phenytoin from plasma obtained from pulse dose pharmacokinetic studies.
Birnbaum, AK; Nelson, MH; Nyhus, PJ; Remmel, RP, 1998
)
0.3
"The pharmacokinetic behavior of fosphenytoin (FOS), the water-soluble prodrug of phenytoin (PHT), has been characterized in normal subjects."( Pharmacokinetics of fosphenytoin in patients with hepatic or renal disease.
Alldredge, BK; Aweeka, FT; Boyer, TD; Eldon, MA; Gambertoglio, JG; Gottwald, MD; Kugler, AR; Pollock, AS; Wright, TL, 1999
)
0.91
" Serial plasma concentrations were measured, and pharmacokinetic parameters were calculated."( Pharmacokinetics of fosphenytoin in patients with hepatic or renal disease.
Alldredge, BK; Aweeka, FT; Boyer, TD; Eldon, MA; Gambertoglio, JG; Gottwald, MD; Kugler, AR; Pollock, AS; Wright, TL, 1999
)
0.63
"Although the differences in pharmacokinetic parameters between the three groups were not statistically significant, these data suggest the need for close clinical monitoring during FOS administration to patients with hepatic or renal disease."( Pharmacokinetics of fosphenytoin in patients with hepatic or renal disease.
Alldredge, BK; Aweeka, FT; Boyer, TD; Eldon, MA; Gambertoglio, JG; Gottwald, MD; Kugler, AR; Pollock, AS; Wright, TL, 1999
)
0.63
" All prior pharmacokinetic studies had the first plasma sample obtained 30 min after IM administration."( Fosphenytoin: pharmacokinetics and tolerance of intramuscular loading doses.
DeToledo, J; Gidal, B; Morgan, RO; Pryor, FM; Ramsay, RE, 2001
)
1.75
" The half-life for conversion of fosphenytoin to phenytoin ranges from 7-15 minutes."( Fosphenytoin: clinical pharmacokinetics and comparative advantages in the acute treatment of seizures.
Fischer, JH; Fischer, PA; Patel, TV, 2003
)
2.04
" dose of fosphenytoin alters the t1/2,z but not the other pharmacokinetic parameters or clinical effects of phenytoin in African children with severe malaria."( Phenytoin pharmacokinetics and clinical effects in African children following fosphenytoin and chloramphenicol coadministration.
Kokwaro, GO; Muchohi, SN; Newton, CR; Ogutu, BR; Otieno, GO, 2002
)
0.96
"We performed a population pharmacokinetic analysis of phenytoin after intravenous administration of fosphenytoin sodium in healthy, neurosurgical, and epileptic subjects, including pediatric patients, and determined the optimal dose and infusion rate for achieving the therapeutic range."( Population pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium in pediatric patients, adult patients, and healthy volunteers.
Kasai, H; Kumagai, Y; Shimasaki, S; Shimizu, K; Tanaka, J, 2013
)
0.83
" The population pharmacokinetic analysis was performed using NONMEM software."( Population pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium in pediatric patients, adult patients, and healthy volunteers.
Kasai, H; Kumagai, Y; Shimasaki, S; Shimizu, K; Tanaka, J, 2013
)
0.62
" Pharmacokinetic parameters of phenytoin, such as total clearance and central and peripheral volume of distribution were influenced by body weight."( Population pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium in pediatric patients, adult patients, and healthy volunteers.
Kasai, H; Kumagai, Y; Shimasaki, S; Shimizu, K; Tanaka, J, 2013
)
0.62
" The present study was performed to investigate the safety, tolerability, and pharmacokinetic profiles of rapid intravenous loading of fosphenytoin in SAH patients."( Safety, Tolerability, and Pharmacokinetics of Fosphenytoin Loading in Patients With Subarachnoid Hemorrhage.
Chun, YI; Ji, M; Kim, DW; Kim, TE,
)
0.59
"Retrospective, population pharmacokinetic analysis."( Fosphenytoin Population Pharmacokinetics in the Acutely Ill Pediatric Population.
Erklauer, J; Galati, M; Moffett, BS; Riviello, JJ; Schmees, LR; Weingarten, MM, 2018
)
1.92
"Population pharmacokinetic analysis was performed with NONMEM v7."( Fosphenytoin Population Pharmacokinetics in the Acutely Ill Pediatric Population.
Erklauer, J; Galati, M; Moffett, BS; Riviello, JJ; Schmees, LR; Weingarten, MM, 2018
)
1.92
" A pharmacokinetic model with two compartments, allometrically scaled fat-free mass on all parameters, and serum creatinine and concomitant phenobarbital use on clearance had the best fit."( Fosphenytoin Population Pharmacokinetics in the Acutely Ill Pediatric Population.
Erklauer, J; Galati, M; Moffett, BS; Riviello, JJ; Schmees, LR; Weingarten, MM, 2018
)
1.92
" The aim of this study was to develop a population pharmacokinetic (PPK) model to describe serum phenytoin concentrations after the intravenous administration of fosphenytoin in adult and elderly epileptic patients."( Population Pharmacokinetic Analysis of Phenytoin After Intravenous Administration of Fosphenytoin in Adult and Elderly Epileptic Patients.
Higuchi, K; Hirakawa, M; Hirota, T; Ieiri, I; Kakara, M; Kashihara, Y; Yamashita, D, 2019
)
0.93

Bioavailability

Fosphenytoin (FPHT; Cerebyx) is well absorbed when given intramuscularly (IM). The relative bioavailability of fospheny toin was 83%.

ExcerptReferenceRelevance
" The objectives of this investigation were to determine the absolute bioavailability and free fraction of PHT after intravenous (i."( Absolute bioavailability of phenytoin after 3-phosphoryloxymethyl phenytoin disodium (ACC-9653) administration to humans.
Brouwer, KL; Donn, KH; Dukes, GE; Jamerson, BD; Messenheimer, JA; Powell, JR,
)
0.13
"41 h-1 and an absolute bioavailability (F) of 100."( Phenytoin prodrug 3-phosphoryloxymethyl phenytoin (ACC-9653): pharmacokinetics in patients following intravenous and intramuscular administration.
Achari, R; Bombassaro, AM; Boucher, BA; Rasmussen, SN; Turlapaty, P; Watridge, CB, 1989
)
0.28
"The bioavailability of phenytoin from ACC-9653 versus intravenously administered sodium phenytoin was determined using a crossover design for intravenous and intramuscular administration of ACC-9653 to healthy volunteers."( Bioavailability of ACC-9653 (phenytoin prodrug).
Browne, TR; Davoudi, H; Donn, KH; Dougherty, CL; Dukes, GE; Evans, B; Evans, JE; Jamerson, B; Kres, J; McEntegart, CM, 1989
)
0.28
"Phenytoin bioavailability was evaluated in beagle dogs after oral and intravenous administrations of sodium phenytoin and two amino acyl esters and a disodium phosphate ester of 3-(hydroxymethyl)phenytoin (three prodrugs of phenytoin)."( Phenytoin prodrugs V: In vivo evaluation of some water-soluble phenytoin prodrugs in dogs.
Stella, VJ; Varia, SA, 1984
)
0.27
"Measurement of the absolute bioavailability of phenytoin (PHT) derived from test doses of phenytoin prodrug (PPD) at therapeutic PHT serum concentrations is complicated by two problems: 1) the area under the serum concentration versus time curve (AUC) produced by a given size of test dose will vary directly with background PHT serum concentration due to the nonlinear pharmacokinetic properties of PHT; 2) PPD is more water soluble than PHT, making renal excretion of PPD more likely."( Bioavailability studies of drugs with nonlinear pharmacokinetics: II. Absolute bioavailability of intravenous phenytoin prodrug at therapeutic phenytoin serum concentrations determined by double-stable isotope technique.
Browne, TR; Davoudi, H; Dougherty, CL; Evans, BA; Evans, JE; Kres, J; McEntegart, C; Miceli, JJ; Quon, C; Szabo, GK, 1993
)
0.29
" The absorption rate appears to be the rate-limiting step in the conversion of fosphenytoin to phenytoin after intramuscular administration (half-life range 22-41 min)."( Fosphenytoin: a novel phenytoin prodrug.
Boucher, BA,
)
1.8
" The relative bioavailability of fosphenytoin was 83%."( Anticonvulsant effect of fosphenytoin in amygdala-kindled rats: comparison with phenytoin.
Ebert, U; Löscher, W; Reissmüller, E, 1998
)
0.88
" When administered intramuscularly, phenytoin is poorly absorbed and can cause hemorrhagic necrosis of the soft tissues at the injection site."( Pediatric use of intravenous and intramuscular phenytoin: lessons learned.
Wheless, JW, 1998
)
0.3
"Fosphenytoin (FPHT; Cerebyx) is well absorbed when given intramuscularly (IM)."( Fosphenytoin: pharmacokinetics and tolerance of intramuscular loading doses.
DeToledo, J; Gidal, B; Morgan, RO; Pryor, FM; Ramsay, RE, 2001
)
3.2
" The bioavailability of the derived phenytoin relative to intravenous phenytoin is approximately 100% following intravenous or intramuscular administration."( Fosphenytoin: clinical pharmacokinetics and comparative advantages in the acute treatment of seizures.
Fischer, JH; Fischer, PA; Patel, TV, 2003
)
1.76
"To compare and evaluate the bioavailability for intravenous fosphenytoin sodium with that of intravenous phenytoin sodium in Japanese subjects."( Bioavailability of intravenous fosphenytoin sodium in healthy Japanese volunteers.
Hiroki, T; Inoue, Y; Kobayashi, S; Shimasaki, S; Shimizu, K; Usui, N, 2013
)
0.92
"To describe the pharmacokinetics of fosphenytoin (FPHT) sodium injection when administered orally, and to determine the relative oral bioavailability (FREL ) of FPHT sodium injection compared with PHT sodium injection based on pharmacokinetic modeling in healthy volunteers."( Relative bioavailability of orally administered fosphenytoin sodium injection compared with phenytoin sodium injection in healthy volunteers.
Acquisto, NM; Forrest, A; Haas, CE; Huntress, JD; Kaucher, KA; Kaufman, DC; Rao, GG, 2015
)
0.95
" Its maximal plasma concentration is achieved within 90-190 min following intramuscular administration with bioavailability being complete after intravenous injection."( The safety and efficacy of fosphenytoin for the treatment of status epilepticus.
Borowicz, KK; Czuczwar, SJ; Popławska, M, 2015
)
0.71
" In conclusion, the use of phosphate ester prodrugs could be an efficient and safe strategy to increase the intranasal bioavailability of poorly soluble drugs."( Intranasal fosphenytoin: The promise of phosphate esters in nose-to-brain delivery of poorly soluble drugs.
Alves, G; Pires, PC; Rodrigues, M; Santos, AO; Santos, LT, 2021
)
1.01
" In a previous study, the intranasal administration of aqueous-based formulations of fosphenytoin led to high but delayed phenytoin bioavailability compared to the intravenous route."( Nose-to-brain delivery of phenytoin and its hydrophilic prodrug fosphenytoin combined in a microemulsion - formulation development and in vivo pharmacokinetics.
Alves, G; Fazendeiro, AC; Pires, PC; Rodrigues, M; Santos, AO, 2021
)
1.08

Dosage Studied

A physician orders fosphenytoin to be administered intramuscularly in a dosage of 30 mL in volume. This clinical policy focuses on 6 critical questions: What laboratory tests are indicated in the otherwise healthy adult patient with a new-onset seizure who has returned to a baseline normal neurologic status?

ExcerptRelevanceReference
" Dosing of fosphenytoin uses phenytoin equivalents (PE) to minimize dosage errors when converting from the conventional formulation."( Fosphenytoin: a novel phenytoin prodrug.
Boucher, BA,
)
1.96
" We studied the PHT dose-response curve for serum PHT and glucose concentrations and several physiological variables."( Phenytoin-induced hyperglycaemia may confound rat cerebroprotection models.
Newman, GC; Qi, H,
)
0.13
" The dosage is expressed as phenytoin sodium equivalents (PE)."( Safety of fosphenytoin sodium.
Benezra, DA; Fierro, LS; Savulich, DH, 1996
)
0.7
" During the 1950s, clinical research established the pediatric dosage of parenteral phenytoin for the treatment of seizures, which was based on the adult dosage adjusted to each child's weight."( Pediatric use of intravenous and intramuscular phenytoin: lessons learned.
Wheless, JW, 1998
)
0.3
" The assay was tested under in vivo conditions by administration of a pulse dose of the stable isotope analogue to a single rat dosed to steady-state with fosphenytoin, a phenytoin prodrug."( A capillary GC-MS method for analysis of phenytoin and [13C3]-phenytoin from plasma obtained from pulse dose pharmacokinetic studies.
Birnbaum, AK; Nelson, MH; Nyhus, PJ; Remmel, RP, 1998
)
0.5
" From our experience, careful and individual dosing of fosphenytoin in this age group can be considered."( Fosphenytoin in infants.
Caviness, VS; Krishnamoorthy, KS; Soman, TB; Takeoka, M, 1998
)
1.99
"3-fold after dosing TAT-59 and 500 microM fosphenytoin, respectively."( Absorption rate limit considerations for oral phosphate prodrugs.
Fleisher, D; Flynn, G; Forsberg, M; Heimbach, T; Leppänen, J; Li, LY; Matsunaga, Y; Oh, DM; Savolainen, J, 2003
)
0.58
" This clinical policy focuses on 6 critical questions: What laboratory tests are indicated in the otherwise healthy adult patient with a new-onset seizure who has returned to a baseline normal neurologic status?Which new-onset seizure patients who have returned to a normal baseline require a head computed tomography (CT) scan in the emergency department (ED)?Which new-onset seizure patients who have returned to normal baseline need to be admitted to the hospital and/or started on an antiepileptic drug?What are effective phenytoin or fosphenytoin dosing strategies for preventing seizure recurrence in patients who present to the ED after having had a seizure with a subtherapeutic serum phenytoin level?What agent(s) should be administered to a patient in status epilepticus who continues to seize after having received benzodiazepine and phenytoin?When should electroencephalographic (EEG) testing be performed in the ED? Recommendations for patient management are provided for each 1 of these topics on the basis of strength of evidence (Level A, B, or C)."( Clinical policy: Critical issues in the evaluation and management of adult patients presenting to the emergency department with seizures.
, 2004
)
0.48
"A physician orders fosphenytoin to be administered intramuscularly in a dosage of 30 mL in volume."( Administer single-site 30-mL intramuscular injection?
Harrington, L, 2005
)
0.66
"This study demonstrates that characterization of pharmacokinetics in a small number of dogs is useful in determining dosage regimens designed to attain targeted concentrations in clinical trials."( Use of IV fosphenytoin pharmacokinetics to determine the loading dose for a clinical trial of canine status epilepticus.
Cloyd, JC; Coles, LD; Leppik, IE; Mishra, U; Patterson, EE; Rivers, Z, 2015
)
0.82
" Various clinical and demographic parameters were analysed, including comorbidities, drug history, seizure aetiology and type, incidence of hypotension/cardiac arrhythmia and the dosing data (ie the total dose, concentration and FOS IV infusion rate)."( Incidence and risk factors of hypotension after intravenous fosphenytoin administration.
Hwang, IG; Kim, DW; Kim, HK; Koh, IS, 2017
)
0.7
" The patient continued to have seizure activity on continuous electroencephalography for which fosphenytoin dosing was increased with subsequent seizure control."( Fosphenytoin-induced purple glove syndrome: A case report.
Blunck, JR; Croom, JE; Fields, RK; Newman, JW, 2017
)
2.12
" Future studies should prospectively verify these observations and characterize dose-response relationships."( Fosphenytoin pre-medication for pediatric extra-operative electrical stimulation brain mapping.
Arya, R; Aungaroon, G; Byars, AW; Greiner, HM; Holland, KD; Horn, PS; Mangano, FT; Zea Vera, A, 2018
)
1.92
" Simulation was performed to determine optimal loading dose and maintenance dosing regimens."( Fosphenytoin Population Pharmacokinetics in the Acutely Ill Pediatric Population.
Erklauer, J; Galati, M; Moffett, BS; Riviello, JJ; Schmees, LR; Weingarten, MM, 2018
)
1.92
" Weight-based dosing was capped at 75 kg."( The association of patient weight and dose of fosphenytoin, levetiracetam, and valproic acid with treatment success in status epilepticus.
Bleck, TP; Chamberlain, JM; Cloyd, JC; Cock, HR; Coles, LD; Conwit, RA; Elm, JJ; Fountain, NB; Kapur, J; Lowenstein, DH; Sathe, AG; Shinnar, S; Silbergleit, R, 2020
)
0.82
"To identify factors associated with low benzodiazepine (BZD) dosing in patients with refractory status epilepticus (RSE) and to assess the impact of BZD treatment variability on seizure cessation."( First-line medication dosing in pediatric refractory status epilepticus.
Abend, NS; Amengual-Gual, M; Anderson, A; Arya, R; Brenton, JN; Carpenter, JL; Chapman, K; Clark, J; Farias-Moeller, R; Gaillard, WD; Gaínza-Lein, M; Glauser, T; Goldstein, JL; Goodkin, HP; Guerriero, RM; Kapur, K; Lai, YC; Loddenkemper, T; McDonough, TL; Mikati, MA; Morgan, LA; Novotny, EJ; Ostendorf, AP; Payne, ET; Peariso, K; Piantino, J; Riviello, JJ; Sannagowdara, K; Tasker, RC; Tchapyjnikov, D; Topjian, A; Vasquez, A; Wainwright, MS; Wilfong, A; Williams, K, 2020
)
0.56
" We used logistic regression modeling to evaluate predictors of low BZD dosing and multivariate Cox regression analysis to assess the impact of low BZD dosing on time to seizure cessation."( First-line medication dosing in pediatric refractory status epilepticus.
Abend, NS; Amengual-Gual, M; Anderson, A; Arya, R; Brenton, JN; Carpenter, JL; Chapman, K; Clark, J; Farias-Moeller, R; Gaillard, WD; Gaínza-Lein, M; Glauser, T; Goldstein, JL; Goodkin, HP; Guerriero, RM; Kapur, K; Lai, YC; Loddenkemper, T; McDonough, TL; Mikati, MA; Morgan, LA; Novotny, EJ; Ostendorf, AP; Payne, ET; Peariso, K; Piantino, J; Riviello, JJ; Sannagowdara, K; Tasker, RC; Tchapyjnikov, D; Topjian, A; Vasquez, A; Wainwright, MS; Wilfong, A; Williams, K, 2020
)
0.56
" Low total BZD dosing was associated with decreased likelihood of Seizure cessation."( First-line medication dosing in pediatric refractory status epilepticus.
Abend, NS; Amengual-Gual, M; Anderson, A; Arya, R; Brenton, JN; Carpenter, JL; Chapman, K; Clark, J; Farias-Moeller, R; Gaillard, WD; Gaínza-Lein, M; Glauser, T; Goldstein, JL; Goodkin, HP; Guerriero, RM; Kapur, K; Lai, YC; Loddenkemper, T; McDonough, TL; Mikati, MA; Morgan, LA; Novotny, EJ; Ostendorf, AP; Payne, ET; Peariso, K; Piantino, J; Riviello, JJ; Sannagowdara, K; Tasker, RC; Tchapyjnikov, D; Topjian, A; Vasquez, A; Wainwright, MS; Wilfong, A; Williams, K, 2020
)
0.56
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
imidazolidine-2,4-dioneAn imidazolidinone with oxo groups at position 2 and 4.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathways (2)

PathwayProteinsCompounds
Fosphenytoin (Antiarrhythmic) Action Pathway479
Fosphenytoin (Antiarrhythmic) Metabolism Pathway42

Bioassays (53)

Assay IDTitleYearJournalArticle
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1347098qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347424RapidFire Mass Spectrometry qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)2019The Journal of biological chemistry, 11-15, Volume: 294, Issue:46
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1347082qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347154Primary screen GU AMC qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347089qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347093qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347092qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347100qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347108qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347099qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347094qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347096qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347090qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347086qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347097qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347425Rhodamine-PBP qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)2019The Journal of biological chemistry, 11-15, Volume: 294, Issue:46
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1347091qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347106qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347101qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347407qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Pharmaceutical Collection2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347104qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID1347105qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347083qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347095qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1745845Primary qHTS for Inhibitors of ATXN expression
AID1347102qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347107qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347103qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1474166Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID625281Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID588218FDA HLAED, lactate dehydrogenase (LDH) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID625284Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID588219FDA HLAED, gamma-glutamyl transferase (GGT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID588215FDA HLAED, alkaline phosphatase increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID625286Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID588216FDA HLAED, serum glutamic oxaloacetic transaminase (SGOT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID625288Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625280Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID588214FDA HLAED, liver enzyme composite activity2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID625289Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625283Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625292Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625291Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID588217FDA HLAED, serum glutamic pyruvic transaminase (SGPT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID1474167Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID625287Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625290Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625282Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625285Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625279Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (247)

TimeframeStudies, This Drug (%)All Drugs %
pre-19908 (3.24)18.7374
1990's72 (29.15)18.2507
2000's60 (24.29)29.6817
2010's68 (27.53)24.3611
2020's39 (15.79)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 63.20

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index63.20 (24.57)
Research Supply Index5.70 (2.92)
Research Growth Index5.51 (4.65)
Search Engine Demand Index105.42 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (63.20)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials35 (13.31%)5.53%
Reviews43 (16.35%)6.00%
Case Studies35 (13.31%)4.05%
Observational7 (2.66%)0.25%
Other143 (54.37%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (8)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
IV Keppra in the Emergency Department for Prevention of Early Recurrent Seizures [NCT00510783]Phase 4158 participants (Actual)Interventional2007-07-31Completed
[NCT00908453]Phase 340 participants (Anticipated)Interventional2009-05-31Completed
Comparison Between Lorazepam, Clonazepam and Clonazepam + Fosphenytoin for the Treatment of Out-of-hospital Generalized Status Epilepticus in Adults Patients [NCT01870024]Phase 3434 participants (Actual)Interventional2013-06-26Completed
Phenytoin as Treatment for Acute Exacerbations of Trigeminal Neuralgia - a Prospective Systematic Study of 30 Patients [NCT03712254]15 participants (Actual)Observational [Patient Registry]2018-11-01Completed
A Pilot Study of NSICU Assessment of Seizure Prophylaxis With Lacosamide [NCT01110187]11 participants (Actual)Interventional2010-05-31Terminated(stopped due to Lack of enrollement)
A Multicenter, Randomized, Blinded, Comparative Effectiveness Study of Fosphenytoin, Valproic Acid, or Levetiracetam in the Emergency Department Treatment of Patients With Benzodiazepine-refractory Status Epilepticus. [NCT01960075]Phase 3478 participants (Actual)Interventional2015-10-31Completed
Double Umbilical Cord Blood Transplantation for Patients With Malignant and Non-Malignant Disorders [NCT00801931]Phase 1/Phase 21 participants (Actual)Interventional2007-09-06Terminated(stopped due to Poor accrual)
Utility of Intravenous Lacosamide Compared With Fosphenytoin in the Treatment of Patients With Frequent Nonconvulsive Seizures [NCT01458522]Phase 274 participants (Actual)Interventional2012-05-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00510783 (1) [back to overview]Number of Participants Who Experienced a Recurrent Seizure After Treatment.
NCT01110187 (2) [back to overview]Number of Adverse Events
NCT01110187 (2) [back to overview]Number of Participants With Seizures
NCT01458522 (11) [back to overview]Number of Predefined Adverse Events (AE) After Treatment Arm 1 Administration
NCT01458522 (11) [back to overview]Number of Subjects Who Required a Second Antiepileptic Drug (AED) to Control Nonconvulsive Seizures (NCS)
NCT01458522 (11) [back to overview]Percentage of Subjects in Whom Study Drug is Withdrawn Early After Treatment With Treatment Arm 1
NCT01458522 (11) [back to overview]Percentage of Subjects Who Experience no Nonconvulsive Seizures (NCS) for 24 Hours Following Treatment With LCM vs. fPHT, as Measured by Continuous Electroencephalography (cEEG) Monitoring.
NCT01458522 (11) [back to overview]Percentage of Subjects Who Require a Rebolus of the Initial Antiepileptic Drugs (AED) to Control Nonconvulsive Seizures (NCS) in the LCM vs fPHT Arms.
NCT01458522 (11) [back to overview]Seizure Burden Change From Baseline to End of Crossover, Excluding Initial Treatment Arm
NCT01458522 (11) [back to overview]Seizure Burden Change From Baseline to End of Initial Treatment
NCT01458522 (11) [back to overview]Change in Functional Status as Measured by the Functional Disability Scale at Day 7 to 9 Postrandomization and Day 30 Post-randomization in the LCM vs fPHT Arms.
NCT01458522 (11) [back to overview]Days in the Intensive Care Unit/Hospital
NCT01458522 (11) [back to overview]Percentage of All Subjects Who Have Had a Seizure, Are on Antiepileptic Drug (AED) Therapy, and Are Alive/Dead at Day 30
NCT01458522 (11) [back to overview]Time of First Bolus to End of Seizures After Initial Treatment Arm, Time From Crossover to End of Seizures in Crossover Treatment Arm
NCT01960075 (17) [back to overview]Length of Hospital Stay
NCT01960075 (17) [back to overview]Length of ICU Stay
NCT01960075 (17) [back to overview]Minutes From Start of Trial Drug Infusion to Termination of Seizures for Patients With Treatment Success
NCT01960075 (17) [back to overview]Number of Participants With Admission to Intensive Care Unit
NCT01960075 (17) [back to overview]Number of Participants With Clinical Cessation of Status Epilepticus - Adjudicated Outcomes Analysis
NCT01960075 (17) [back to overview]Number of Participants With Clinical Cessation of Status Epilepticus - Intention to Treat
NCT01960075 (17) [back to overview]Number of Participants With Clinical Cessation of Status Epilepticus - Per-protocol Analysis
NCT01960075 (17) [back to overview]Number of Participants With Safety Outcome: Acute Anaphylaxis
NCT01960075 (17) [back to overview]Number of Participants With Safety Outcome: Acute Respiratory Depression
NCT01960075 (17) [back to overview]Number of Participants With Safety Outcome: Acute Seizure Recurrence
NCT01960075 (17) [back to overview]Number of Participants With Safety Outcome: Death
NCT01960075 (17) [back to overview]Number of Participants With Safety Outcome: Endotracheal Intubation
NCT01960075 (17) [back to overview]Number of Participants With Safety Outcome: Hepatic Transaminase or Ammonia Elevations
NCT01960075 (17) [back to overview]Number of Participants With Safety Outcome: Life Threatening Hypotension
NCT01960075 (17) [back to overview]Number of Participants With Safety Outcome: Life-threatening Cardiac Arrhythmia
NCT01960075 (17) [back to overview]Number of Participants With Safety Outcome: Purple Glove Syndrome
NCT01960075 (17) [back to overview]Number of Participants With Seizure Cessation Within 20 Minutes for Patients With Treatment Success

Number of Participants Who Experienced a Recurrent Seizure After Treatment.

Recurrent seizure is defined as a seizure within 24 hours of treatment in the Emergency Department. (NCT00510783)
Timeframe: 24 hours

Interventionparticipants (Number)
Phenytoin/Fosphenytoin2
Levetiracetam3

[back to top]

Number of Adverse Events

The primary outcome measure is the incidence of clinical adverse events. These will be followed by daily clinical observations during the hospital stay. Subjects will be evaluated for e.g., seizures, fever, neurological changes, cardiovascular, hematologic and dermatologic abnormalities, liver failure, renal failure, and death; EKGs will be requested as per ICU routines through day 7. (NCT01110187)
Timeframe: baseline to 7 days

Interventionnumber of events experienced (Number)
IV LCM12
IV fPHT21

[back to top]

Number of Participants With Seizures

Number of seizures in the first 72 hours based on EEG recording (NCT01110187)
Timeframe: baseline to 72 hours

Interventionnumber of participants with seizures (Number)
IV LCM0
IV fPHT0

[back to top]

Number of Predefined Adverse Events (AE) After Treatment Arm 1 Administration

Number of predefined adverse events (AE) after treatment arm 1 administration. These predefined adverse events include Patients with at least one AE of interest, Cardiac disorders, investigations, suspected hypersensitivity reactions, vascular disorders, and hypotension. (NCT01458522)
Timeframe: 24 hours

InterventionNumber of predefined AEs (Number)
LCM 400mg4
fPHT 20mg PE/kg5

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Number of Subjects Who Required a Second Antiepileptic Drug (AED) to Control Nonconvulsive Seizures (NCS)

Number of subjects who required a second antiepileptic drug (AED) to control nonconvulsive seizures (NCS) (NCT01458522)
Timeframe: 24-26 hours

InterventionParticipants (Count of Participants)
LCM First, Then fPHT15
fPHT First, Then LCM10

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Percentage of Subjects in Whom Study Drug is Withdrawn Early After Treatment With Treatment Arm 1

Percentage of subjects in whom study drug is withdrawn early after treatment with treatment arm 1 (NCT01458522)
Timeframe: baseline to end of treatment arm 1

InterventionParticipants (Count of Participants)
LCM Treatment2
fPHT Treatment3

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Percentage of Subjects Who Experience no Nonconvulsive Seizures (NCS) for 24 Hours Following Treatment With LCM vs. fPHT, as Measured by Continuous Electroencephalography (cEEG) Monitoring.

Percentage of subjects who experience no nonconvulsive seizures (NCS) for 24 hours (after the 2-hour observation-only period) following treatment with LCM vs. fPHT, as measured by continuous electroencephalography (cEEG) monitoring with blinded review. (NCT01458522)
Timeframe: 24 hours

InterventionParticipants (Count of Participants)
LCM 400mg19
fPHT 20mg PE/kg22

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Percentage of Subjects Who Require a Rebolus of the Initial Antiepileptic Drugs (AED) to Control Nonconvulsive Seizures (NCS) in the LCM vs fPHT Arms.

The percentage of subjects who require a rebolus of the initial antiepileptic drug (AED) to control nonconvulsive seizures (NCS) in the LCM vs fPHT arms. (NCT01458522)
Timeframe: 24 hours

InterventionParticipants (Count of Participants)
LCM 400mg16
fPHT 20mg PE/kg13

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Seizure Burden Change From Baseline to End of Crossover, Excluding Initial Treatment Arm

Absolute change defined as the number of minutes of ESz activity per hour before treatment and at the end of the second treatment arm. This measure does not evaluate seizure activity in the first treatment arm. If less than 1 hour of recording time is available, seizure time will be extrapolated to 1 hour. (NCT01458522)
Timeframe: baseline, 26-68 hours

Interventionmin/hour (Mean)
LCM First, Then fPHT-0.78
fPHT First, Then LCM-0.83

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Seizure Burden Change From Baseline to End of Initial Treatment

Absolute change in seizure time (defined as the number of minutes of electrographic seizure (ESz) activity per hour) before treatment and at the end of the first treatment arm. If less than 1 hour of recording time is available, seizure time will be extrapolated to 1 hour. The maximum amount of time that can be used to determine baseline seizure time is 6 hours. (NCT01458522)
Timeframe: Baseline, 24 hours

Interventionmin/hour (Mean)
LCM 400mg-0.58
fPHT 20mg PE/kg-0.54

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Change in Functional Status as Measured by the Functional Disability Scale at Day 7 to 9 Postrandomization and Day 30 Post-randomization in the LCM vs fPHT Arms.

Change in functional status as measured by the Functional Disability Scale, using a 0-29 rating (0=w/o disability; 29=extreme vegetative state) at Day 7 to 9 postrandomization and Day 30 post-randomization in the LCM first, then fPHT versus fPHT first, then LCM arms. Data was analyzed in a manner consistent with determining if one treatment arm resulted in a greater change in functional status than the other. (NCT01458522)
Timeframe: Baseline to day 7-9, baseline to day 30

,
Interventionunits on a scale (Mean)
Change from baseline to day 7-9Change from baseline to day 30
fPHT First, Then LCM0.3-3.7
LCM First, Then fPHT-4.1-8.5

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Days in the Intensive Care Unit/Hospital

Data was acquired in a manner consistent with determining if one treatment arm (LCM first, then fPHT versus fPHT first, then LCM) resulted in more days of hospitalization than the other over the course of the study. (NCT01458522)
Timeframe: initial bolus to end of study

,
Interventiondays (Mean)
Days in ICUDays in hospital
fPHT First, Then LCM6.512.5
LCM First, Then fPHT7.412.7

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Percentage of All Subjects Who Have Had a Seizure, Are on Antiepileptic Drug (AED) Therapy, and Are Alive/Dead at Day 30

Percentage of all subjects who have had a seizure, are on antiepileptic drug (AED) therapy, and are alive and dead at day 30. Data was acquired in a manner consistent with determining if one treatment arm (LCM first, then fPHT versus fPHT first, then LCM) resulted in a greater effect on seizures, antiepileptic drug (AED) use, and survival at day 30 after the acute treatment period. The acute treatment period could range from 6 to 30 hours. (NCT01458522)
Timeframe: both acute treatment periods to 30 days

,
Interventionpercentage of participants (Number)
any seizure within 30 days after acute tx periodAED use within 30 days after acute tx periodDied within 30 days after randomization
fPHT First, Then LCM38.974.016.0
LCM First, Then fPHT27.482.215.5

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Time of First Bolus to End of Seizures After Initial Treatment Arm, Time From Crossover to End of Seizures in Crossover Treatment Arm

Time of first bolus to end of seizures after initial treatment arm, time from crossover to end of seizures in crossover treatment arm (NCT01458522)
Timeframe: time of first bolus to end of seizures after initial treatment arm, time from crossover to end of seizures in crossover treatment arm

,
Interventionhours (Mean)
Initial TreatmentCrossover Treatment
fPHT First, Then LCM9.81.7
LCM First, Then fPHT8.48.2

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Length of Hospital Stay

Length of hospital stay in days (NCT01960075)
Timeframe: length of hospital stay

Interventiondays (Median)
Fosphenytoin (FOS)3
Valproic Acid3
Levetiracetam3

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Length of ICU Stay

Length of stay is determined by the number of calendar days after the day of ED arrival until hospital discharge or subject end-of-study. (NCT01960075)
Timeframe: number of calendar days after the day of ED arrival until hospital discharge or subject end-of-study

Interventiondays (Median)
Fosphenytoin (FOS)1
Valproic Acid1
Levetiracetam1

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Minutes From Start of Trial Drug Infusion to Termination of Seizures for Patients With Treatment Success

The time to termination of seizures is the interval from the start of study drug infusion to cessation of clinically apparent seizure in those who meet the primary outcome. (NCT01960075)
Timeframe: start of drug infusion to seizure cessation

Interventionminutes (Median)
Fosphenytoin (FOS)11.7
Valproic Acid7.0
Levetiracetam10.5

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Number of Participants With Admission to Intensive Care Unit

ICU admission is recorded as occurring only if the ICU is the initial inpatient unit for the patient. (NCT01960075)
Timeframe: Admission to intensive care unit after start of study drug infusion, where the ICU is the initial inpatient unit for the patient

InterventionParticipants (Count of Participants)
Fosphenytoin (FOS)70
Valproic Acid71
Levetiracetam87

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Number of Participants With Clinical Cessation of Status Epilepticus - Adjudicated Outcomes Analysis

Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. The Adjudicated outcomes analysis is different from Outcome measure 1 because a central clinical phenomenology core of four neurologists adjudicated from the medical records the time to seizure cessation, the time in status epilepticus before trial-drug initiation, and the cause of the seizure. For each enrollment, two neurologists from this core group conducted independent initial reviews and then determined a consensus or consulted a third adjudicator, as needed. Adjudicators were unaware of the treatment assignments and made determinations by medical record review. (NCT01960075)
Timeframe: Within 60 minutes after the start of study drug infusion

InterventionParticipants (Count of Participants)
Fosphenytoin (FOS)57
Valproic Acid60
Levetiracetam67

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Number of Participants With Clinical Cessation of Status Epilepticus - Intention to Treat

Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. Intention to treat (NCT01960075)
Timeframe: Within 60 minutes after the start of study drug infusion

InterventionParticipants (Count of Participants)
Fosphenytoin (FOS)53
Valproic Acid56
Levetiracetam68

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Number of Participants With Clinical Cessation of Status Epilepticus - Per-protocol Analysis

Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. Per-protocol analysis (NCT01960075)
Timeframe: Within 60 minutes after the start of study drug infusion

InterventionParticipants (Count of Participants)
Fosphenytoin (FOS)37
Valproic Acid43
Levetiracetam51

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Number of Participants With Safety Outcome: Acute Anaphylaxis

Acute anaphylaxis is defined as a clinical presentation consistent with life threatening allergic reaction occurring within 6 hours of the start of study drug infusions and manifested as urticaria in combination with either (1) a systolic blood pressure of < 90 mmHg sustained for greater than 5 minutes, or (2) objective evidence of airway obstruction, and for which the patient was treated with antihistamines and/or steroids. (NCT01960075)
Timeframe: within 6 hours of the start of study drug infusions

InterventionParticipants (Count of Participants)
Fosphenytoin (FOS)0
Valproic Acid0
Levetiracetam0

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Number of Participants With Safety Outcome: Acute Respiratory Depression

Respiratory depression is defined as impairment of ventilation or oxygenation necessitating definitive endotracheal intubation and mechanical ventilation. It is distinct from intubations performed only for airway protection in those with decreased levels of consciousness. It does not include those getting only supraglottic airways or transient bag-valve-mask support. (NCT01960075)
Timeframe: 24 hours

InterventionParticipants (Count of Participants)
Fosphenytoin (FOS)16
Valproic Acid10
Levetiracetam12

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Number of Participants With Safety Outcome: Acute Seizure Recurrence

acute seizure recurrence 60 minutes to 12 hours after start of study drug infusion (NCT01960075)
Timeframe: 60 minutes to 12 hours after start of study drug infusion

InterventionParticipants (Count of Participants)
Fosphenytoin (FOS)14
Valproic Acid14
Levetiracetam16

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Number of Participants With Safety Outcome: Death

Safety outcome: Death (NCT01960075)
Timeframe: 30 days

InterventionParticipants (Count of Participants)
Fosphenytoin (FOS)3
Valproic Acid2
Levetiracetam7

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Number of Participants With Safety Outcome: Endotracheal Intubation

Endotracheal intubation within 60 minutes of start of study drug infusion (NCT01960075)
Timeframe: within 60 minutes of start of study drug infusion

InterventionParticipants (Count of Participants)
Fosphenytoin (FOS)33
Valproic Acid21
Levetiracetam30

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Number of Participants With Safety Outcome: Hepatic Transaminase or Ammonia Elevations

Safety outcome: Hepatic transaminase or ammonia elevations (NCT01960075)
Timeframe: 24 hours

InterventionParticipants (Count of Participants)
Fosphenytoin (FOS)0
Valproic Acid1
Levetiracetam1

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Number of Participants With Safety Outcome: Life Threatening Hypotension

Life-threatening hypotension within 60 minutes of the start of study drug infusion (NCT01960075)
Timeframe: within 60 minutes of the start of study drug infusion

InterventionParticipants (Count of Participants)
Fosphenytoin (FOS)4
Valproic Acid2
Levetiracetam1

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Number of Participants With Safety Outcome: Life-threatening Cardiac Arrhythmia

Life-threatening cardiac arrhythmia within 60 minutes of the start of study drug infusion (NCT01960075)
Timeframe: within 60 minutes of the start of study drug infusion

InterventionParticipants (Count of Participants)
Fosphenytoin (FOS)0
Valproic Acid0
Levetiracetam1

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Number of Participants With Safety Outcome: Purple Glove Syndrome

Purple glove syndrome is defined as the presence of all three of the findings of the objective edema: discoloration, and pain in the distal extremity in which study drug was administered, with or without known extravasation, and for which there is no other evident etiology. (NCT01960075)
Timeframe: 24 hours

InterventionParticipants (Count of Participants)
Fosphenytoin (FOS)0
Valproic Acid0
Levetiracetam0

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Number of Participants With Seizure Cessation Within 20 Minutes for Patients With Treatment Success

Number of participants with seizure cessation within 20 minutes of study drug initiation for patients with treatment success. This outcome measure was only reported in the Supplementary materials to the Primary Paper. (NCT01960075)
Timeframe: within 20 minutes

InterventionParticipants (Count of Participants)
Fosphenytoin (FOS)43
Valproic Acid43
Levetiracetam53

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