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Population Pharmacokinetics of Phenytoin in Japanese Patients with Epilepsy: Analysis with a Dose-Dependent Clearance Model.

1996; Pharmaceutical Society of Japan; Volume: 19; Issue: 3 Linguagem: Inglês

10.1248/bpb.19.444

1347-5215

Atsuko ODANI, Yukiya Hashimoto, Kazunobu Takayanagi, Yuko OTSUKI, Toshiko Koue, Mikihisa Takano, Masato Yasuhara, Haruo Hattori, Kenshi Furusho, Ken‐ichi Inui,

Drug Transport and Resistance Mechanisms

The population pharmacokinetic parameters of phenytoin were estimated using routine therapeutic drug monitoring data from 116 epileptic patients. The 531 serum concentration values at steady-state after repetitive oral administration were analyzed using a 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 phenytoin. The volume of distribution (V) was estimated to be 1.23l/kg in a typical 42-kg patient, assuming that the bioavailability of orally administered phenytoin is 100%. The maximal elimination rate (Vmax) and the Michaelis-Menten constant (Km) were 9.80mg/d/kg and 9.19μg/ml, respectively. The parameter of power function of weight to adjust V and Vmax was estimated to be 0.463. In addition, Km for phenytoin appeared to be 16% increased in patients receiving zonisamide concurrently. The population pharmacokinetic parameters of phenytoin will be useful for designing dosage regimens in epileptic patients.