Biomaterial Database

[NONMEM approach for estimating population pharmacokinetic parameters of phenytoin in Chinese epileptics]. 1995

J Z Rui, and M H Cai, and X M Chu, and G Chen

Department of Clinical Pharmacology, General Hospital of Nanjing Armed Forces.

Routine clinical pharmacokinetic data collected from epileptic out-patients who received phenytoin (PHT) were analysed to estimate population pharmacokinetic parameters. There were 258 steady-state serum phenytoin concentrations and associated dosage (mg.d-1) from 161 out-patients. The data were analysed using NONMEM program. The influence of body weight, drug combinations and sex on the maximum elimination rate (Vm) and age on the Michaelis-Menten constant (Km) were investigated. The Vm and Km of phenytoin in a 60 kg adult out-patient, without combination with other drugs (phenobarbital, clonazepam or diazepam) were estimated to be 439 mg.d-1 and 6.21 micrograms.ml-1, respectively. The best function adjusts Vm to the 0.57 power in proportion to body weight. The Km for patients less than 15 years old was 7% less than that for adults. The Vm of patients treated with phenytoin combined with phenobarbital, clonazepam or diazepam will increase 8.4 mg.d-1.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D010672	Phenytoin	An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.	Diphenylhydantoin,Fenitoin,Phenhydan,5,5-Diphenylhydantoin,5,5-diphenylimidazolidine-2,4-dione,Antisacer,Difenin,Dihydan,Dilantin,Epamin,Epanutin,Hydantol,Phenytoin Sodium,Sodium Diphenylhydantoinate,Diphenylhydantoinate, Sodium
D002648	Child	A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL.	Children
D002675	Child, Preschool	A child between the ages of 2 and 5.	Children, Preschool,Preschool Child,Preschool Children
D004827	Epilepsy	A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)	Aura,Awakening Epilepsy,Seizure Disorder,Epilepsy, Cryptogenic,Auras,Cryptogenic Epilepsies,Cryptogenic Epilepsy,Epilepsies,Epilepsies, Cryptogenic,Epilepsy, Awakening,Seizure Disorders
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000293	Adolescent	A person 13 to 18 years of age.	Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults