caa a22 4500 475818121 CHVBK 20180406123814.0 cr unu---uuuuu 170329e20000401xx s 000 0 eng 10.1007/s002280050722 doi (NATIONALLICENCE)springer-10.1007/s002280050722 Lack of differences in diclofenac (a substrate for CYP2C9) pharmacokinetics in healthy volunteers with respect to the single CYP2C9 * 3 allele [Elektronische Daten] [J. Shimamoto, I. Ieiri, A. Urae, M. Kimura, S. Irie, T. Kubota, K. Chiba, T. Ishizaki, K. Otsubo, S. Higuchi] Objectives: Evidence exists to suggest that diclofenac is metabolised by CYP2C9. The present study was undertaken in order to evaluate the effect of the single CYP2C9*3 variant on drug metabolism using diclofenac as a probe drug. Methods: A single dose of diclofenac was administered orally to 12 healthy subjects in whom the genotype of CYP2C9 had been determined previously. The disposition kinetics of diclofenac were compared between homozygotes for the wild type (CYP2C9*1/*1, n=6) and heterozygotes for the Leu359 variant (CYP2C9*1/*3, n=6). Results: For diclofenac, the following kinetic parameters were observed in the CYP2C9*1/*1 and CYP2C9*1/*3 subjects, respectively (mean ± SD): apparent oral clearance (ml/kg/h) 355.8 ± 56.9 and 484.4 ± 155.3; area under plasma concentration-time curve (μg h/ml) 2.7 ± 0.7 and 1.9 ± 0.6. The formation clearance of 4′-hydroxydiclofenac (ml/kg/h) was 63.6 ± 19.1 in the CYP2C9*1/*1 subjects compared with 75.9 ± 27.6 in the CYP2C9*1/*3 subjects. There were no significant differences in any of the kinetic parameters for either diclofenac disposition or formation clearance of 4′-hydroxydiclofenac between the two genotype groups. Conclusion: Since the disposition kinetics of diclofenac does not change in subjects with the single CYP2C9*3 mutant allele, it is suggested that the effects of CYP2C9 polymorphisms on the drug metabolism tend to be substrate specific. Springer-Verlag Berlin Heidelberg, 2000 Key words CYP2C9 nationallicence Genetic polymorphism nationallicence Diclofenac nationallicence Shimamoto J. Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan, JP aut Ieiri I. Department of Hospital Pharmacy, Faculty of Medicine, Tottori University, Nishi-machi 36-1, Yonago, 683-8504, Japan e-mail: ieiri-ttr@umin.ac.jp Tel.: +81-859-348349; Fax: +81-859-348087, JP aut Urae A. Kyushu Clinical Pharmacology Research Clinic, Fukuoka, Japan, JP aut Kimura M. Kyushu Clinical Pharmacology Research Clinic, Fukuoka, Japan, JP aut Irie S. Kyushu Clinical Pharmacology Research Clinic, Fukuoka, Japan, JP aut Kubota T. Research Testing Department, SRL, Inc., Tokyo, Japan, JP aut Chiba K. Laboratory of Biochemical Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, Chiba University, Chiba, Japan, JP aut Ishizaki T. Department of Pharmacology and Therapeutics, Graduate School of Clinical Pharmacy, Kumamoto University, Kumamoto, Japan, JP aut Otsubo K. Department of Hospital Pharmacy, Faculty of Medicine, Tottori University, Tottori, Japan, JP aut Higuchi S. Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan, JP aut https://doi.org/10.1007/s002280050722 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050722 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Shimamoto J. Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan, JP aut NATIONALLICENCE 700 1- Ieiri I. Department of Hospital Pharmacy, Faculty of Medicine, Tottori University, Nishi-machi 36-1, Yonago, 683-8504, Japan e-mail: ieiri-ttr@umin.ac.jp Tel.: +81-859-348349; Fax: +81-859-348087, JP aut NATIONALLICENCE 700 1- Urae A. Kyushu Clinical Pharmacology Research Clinic, Fukuoka, Japan, JP aut NATIONALLICENCE 700 1- Kimura M. Kyushu Clinical Pharmacology Research Clinic, Fukuoka, Japan, JP aut NATIONALLICENCE 700 1- Irie S. Kyushu Clinical Pharmacology Research Clinic, Fukuoka, Japan, JP aut NATIONALLICENCE 700 1- Kubota T. Research Testing Department, SRL, Inc., Tokyo, Japan, JP aut NATIONALLICENCE 700 1- Chiba K. Laboratory of Biochemical Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, Chiba University, Chiba, Japan, JP aut NATIONALLICENCE 700 1- Ishizaki T. Department of Pharmacology and Therapeutics, Graduate School of Clinical Pharmacy, Kumamoto University, Kumamoto, Japan, JP aut NATIONALLICENCE 700 1- Otsubo K. Department of Hospital Pharmacy, Faculty of Medicine, Tottori University, Tottori, Japan, JP aut NATIONALLICENCE 700 1- Higuchi S. Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan, JP aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer