文章基本信息

标题：Population Analysis of the Dose-Dependent Pharmacokinetics of Zonisamide in Epileptic Patients
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作者：Yukiya HASHIMOTO ; Atsuko ODANI ; Yusuke TANIGAWARA 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1994
卷号：17
期号：2
页码：323-326
DOI：10.1248/bpb.17.323
出版社：The Pharmaceutical Society of Japan
摘要：The pharmacokinetics of zonisamide was studied using routine therapeutic drug monitoring data from 68 epileptic patients. The 266 serum concentration data at steady-state after repetitive oral administration were analyzed using the nonlinear mixed effects model (NONMEM) program designed for estimation of population pharmacokinetic parameters. A one-compartment model with dose-dependent clearance was used for the pharmacokinetic analysis of zonisamide. The volume of distribution (V) was estimated to be 1.27 l/kg in a typical 33-kg patient, assuming that the bioavailability of orally administered zonisamide is 100%. The maximal daily dose to be cleared (V_max) and the concentration giving half maximal clearance (a Michaelis-Menten constant) was 27.6 mg/d/kg and 45.9 μg/ml, respectively. The parameter of a power function of weight to adjust V and V_max was estimated to be 0.741. In addition, V_max for zonisamide appears to be 13% increased in patients receiving carbamazepine concurrently. The population pharmacokinetic parameters of zonisamide will be useful for designing dosage regimens in epileptic patients.
关键词：zonisamide;population pharmacokinetics;dose-dependent kinetics;carbamazepine;drug interaction;NONMEM