Hamasaki H

References (1)

Title : The effect of carboxylesterase 1 (CES1) polymorphisms on the pharmacokinetics of oseltamivir in humans - Suzaki_2013_Eur.J.Clin.Pharmacol_69_21
Author(s) : Suzaki Y , Uemura N , Takada M , Ohyama T , Itohda A , Morimoto T , Imai H , Hamasaki H , Inano A , Hosokawa M , Tateishi M , Ohashi K
Ref : European Journal of Clinical Pharmacology , 69 :21 , 2013
Abstract : PURPOSE: The aim of this study was to examine whether carboxylesterase 1 (CES1A) genetic polymorphisms affect the pharmacokinetics of oseltamivir.
METHODS: Thirty healthy Japanese male and female subjects ranging in age from 20 to 36 years voluntarily participated in this study. These subjects were administered a single 75-mg dose of oseltamivir (Tamiflu(R)), and blood samples were collected predose and up to 24 h after oseltamivir administration. Oseltamivir and its active metabolite, oseltamivir carboxylate, were measured by liquid chromatography-time of flight/mass spectrometry with solid-phase extraction. The CES1A diplotypes [a combination of haplotypes A (CES1A3-CES1A1), B (CES1A2-CES1A1), C (CES1A3-CES1A1variant), and D (CES1A2-CES1A1variant)] were determined by PCR-restriction fragment length polymorphism analysis and direct sequencing.
RESULTS: All subjects completed the study according to the protocol, and no clinically meaningful adverse events were attributable to the administration of oseltamivir. No significant differences in the pharmacokinetic parameters of oseltamivir and oseltamivir carboxylate were observed according to CES1A genotype. In one subject, the peak concentration and area under the concentration-time curve (AUC) of oseltamivir were approximately tenfold higher than the mean values of the other subjects.
CONCLUSIONS: In our study, the known interindividual variability in oseltamivir metabolism was not explained by CES1A genetic polymorphisms, but are likely the result of other factors. While one subject was found to exhibit an approximate tenfold higher AUC than the other subjects, no abnormal behaviors were associated with the increased oseltamivir plasma concentrations. Further studies are required to reveal the cause of individual differences in CES1A metabolism and the abnormal behavioral effects of oseltamivir.
ESTHER : Suzaki_2013_Eur.J.Clin.Pharmacol_69_21
PubMedSearch : Suzaki_2013_Eur.J.Clin.Pharmacol_69_21
PubMedID: 22673926