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

Ebrahim Salehifar; Madjid Zohrabi; Somayyeh Eshghi; Madjid Saeedi; Pooneh Ebrahimi

doi:10.22037/ijpr.2010.786

IJ Pharmaceutical Research

Current Issue All Issues In Press Accepted Manuscripts Search

Journal Information Editors & Boards Indexing and Listing Sources Journal Metrics Open Peer Review (OPR)Publication Ethics and Malpractice Statement Reviewer and AE Registration Form Contact Us Support

APC

Authors Guide Submit Manuscript

https://doi.org/10.22037/ijpr.2010.786

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

Author(s):

Ebrahim Salehifar^1,*,

Madjid Zohrabi²,

Somayyeh Eshghi³,

Madjid Saeedi⁴,

Pooneh Ebrahimi⁵

1Department of Clinical Pharmacy, Faculty of Pharmacy and Pharmaceutical Research Center, Mazandaran University of Medical Sciences, Sari, Iran

2Department of Neurosurgery, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

3Faculty of Pharmacy and Pharmaceutical Research Center, Mazandaran University of Medical Sciences, Sari, Iran

4Department of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Research Center, Mazandaran University of Medical Sciences, Sari, Iran

5Gorgan University of Agricultural Sciences and Natural Resources, Higher Education Center, Gonbad, Iran

IJ Pharmaceutical Research:Vol. 8, issue 1; 37-45

Published online:Nov 20, 2010

Article type:Research Article

Received:Jan 01, 2008

Accepted:Jul 01, 2008

How to Cite:Ebrahim SalehifarMadjid ZohrabiSomayyeh EshghiMadjid SaeediPooneh EbrahimiDifferent pharmacokinetic parameters of phenytoin in Iranian Outpatients: Need to optimize the current dosage administration.Iran J Pharm Res.8(1):e128613.https://doi.org/10.22037/ijpr.2010.786.

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 (CL_int) 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 CL_int 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

Clearance

Michaelis-Menten constant (Km)

maximum rate of metabolism (Vm)

Pharmacokinetics

Phenytoin

comments

Crossmark

Checking

Share on

Comments

Number of Comments:0

Cited by

CrossRef 0

Metrics

Get Permission (article level)

Purchasing Reprints

Copyright Clearance Center (CCC) handles bulk orders for article reprints for Brieflands. To place an order for reprints, please click here ( https://www.copyright.com/landing/reprintsinquiryform/ ). Clicking this link will bring you to a CCC request form where you can provide the details of your order. Once complete, please click the ‘Submit Request’ button and CCC’s Reprints Services team will generate a quote for your review.

Search Relations

Author(s):

Ebrahim Salehifar:[PubMed][Scholar]
Madjid Zohrabi:[PubMed][Scholar]
Somayyeh Eshghi:[PubMed][Scholar]
Madjid Saeedi:[PubMed][Scholar]
Pooneh Ebrahimi:[PubMed][Scholar]