Different pharmacokinetic parameters of phenytoin in Iranian Outpatients: Need to optimize the current dosage administration چاپ
نوشته شده توسط Administrator   
یکشنبه, 29 اسفند 1389 ساعت 14:12

Ebrahim Salehifar , Madjid Zohrabi , Somayyeh Eshghi,

Madjid Saeedi and Pooneh Ebrahimie

 

 

Copyright © 2009 by School of Pharmacy

Shaheed Beheshti University of Medical Sciences and Health Services

Iranian Journal of Pharmaceutical Research (2009), 8 (1): 37-45

Received: January 2008

Accepted: July 2008

Original Article



Different pharmacokinetic parameters of phenytoin in Iranian Outpatients: Need to optimize the current dosage administration


Ebrahim Salehifar , Madjid Zohrabi , Somayyeh Eshghi

Madjid Saeedid and Pooneh Ebrahimie


Department of Clinical Pharmacy, Faculty of Pharmacy and Pharmaceutical Research Center, Mazandaran University of Medical Sciences, Sari, Iran. bDepartment of Neurosurgery, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

Faculty of Pharmacy and Pharmaceutical Research Center, Mazandaran University of Medical Sciences, Sari, Iran. dDepartment of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Research Center, Mazandaran University of Medical Sciences, Sari, Iran. eGorgan University of Agricultural Sciences and Natural Resources, Higher Education Center, Gonbad, Iran


Abstract

Dose-dependent pharmacokinetic of phenytoin necessitates the estimation of the maximum rate of metabolism (Vm) and the Michaelis-Menten constant (Km) in a concerned population. The aim of this study was to determine the pharmacokinetic parameters of phenytoin in a sample of Iranian patients to optimize the antiepileptic pharmacotherapy. Fourty patients who received a constant dose of phenytoin for at least three weeks were included in the study. Steady-state trough serum concentration has been used to determine the Vm and Km by Vozeh-Sheiner (orbit-graph) method. Mann-Whitney U-test and chi-square test have been used to compare the quantitative and qualitative variables respectively. Only half of the patients were in the therapeutic range. Mean Vm and mean Km were 6.12±1.01 mg/kg/day and 5.90±1.26 mg/l respectivly with significant differences [95% confidence interval of difference with the reported to mean values of 7 mg/Kg/day for Vm and 4 mg/l for Km interval -0.88 (-1.2 to 0.55) and +1.9 (1.49 to 2.31) respectively]. A trend towards higher clearance (CL) and intrinsic clearance (CLint) were observed in patients on polytherapy with phenobarbital compared to those on phenytoin monotherapy. Advanced age was inversely associated with the values of Vm and CLint in the group on monotherapy. Considering the observed lower Vm and higher Km, our population may have a lower metabolic capacity for metabolism of phenytoin, and using the estimates of Vm and Km obtained this study could help the clinicians to individualize antiepileptic therapy. In addition, the results of this study may propose that the expression of CYP2C9 and CYP2C19, as two main pathways of phenytoin metabolism, may be lower in iranians than the other populations, and phenotyping/genotyping studies of these pathways are recommended


Keywords: Phenytoin; Pharmacokinetics; maximum rate of metabolism (Vm); Michaelis-Menten constant (Km); Clearance


یادداشت های بازدید کننده گان
لطفا برای نوشتن یادداشت یا وارد سایت شوید یا ثبت نام نمایید

آخرین بروز رسانی در یکشنبه, 29 اسفند 1389 ساعت 14:27
تعداد مشاهده مطلب : 8133