Association between Sex Differences and the Pharmacokinetics of Repaglinide among a Malaysian Population

Ruzilawati Abu  Bakar; Mohd Suhaimi Ab  Wahab; Imran  Ahmad; Gan Siew  Hua

doi:10.4236/pp.2011.24042

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PP Vol.2 No.4 , October 2011

Association between Sex Differences and the Pharmacokinetics of Repaglinide among a Malaysian Population

Ruzilawati Abu Bakar, Mohd Suhaimi Ab Wahab, Imran Ahmad, Gan Siew Hua

Abstract: This study was conducted to evaluate the effect of sex differences on the pharmacokinetics of repaglinide in healthy subjects. One hundred twenty one healthy volunteers (61 male and 60 female; aged 18 - 50 years) were included in the study. Subjects were administered a single 4-mg repaglinide oral dose. Blood samples were taken at 0, 30, 60, 120, 180 and 240 min. Serum repaglinide levels were determined by a high-performance liquid chromatography (HPLC) method. Subjects were also genotyped by polymerase chain reactions - restriction fragment length polymorphisms (PCR-RFLP) for CYP3A4*4, *5 and *18 alleles and by an allele-specific multiplex PCR for CYP2C8*2, *3, *4 and *5 alleles. The pharmacokinetics of repaglinide were comparable between male and female subjects. The mean clearance (CL) of repaglinide was 16.0% lower (p = 0.03), the mean area under the serum concentration-time curve (AUC) was 12.8% higher (p = 0.04) and the peak serum concentration (Cmax) was 13.2% higher (p = 0.03) in females compared to male subjects. The mean rate of elimination (kel) and mean CL of repaglinide were 47.67% (p = 0.03) higher and 29.25% (p = 0.03) higher, respectively, in male subjects having CYP2C8*5 allele compared to female subjects. We also found that the mean half-life (t1/2) of repaglinide was 42.43% higher (p = 0.03), and the mean AUC was 35.83% higher (p = 0.03) in female subjects when compared to the male subjects having CYP2C8*5 allele. Sex differences significantly influence the pharmacokinetics of repaglinide.

Keywords: Sex Differences, CYP2C8, CYP3A4, Polymorphisms, Repaglinide

Cite this paper: nullR. Bakar, M. Wahab, I. Ahmad and G. Hua, "Association between Sex Differences and the Pharmacokinetics of Repaglinide among a Malaysian Population," Pharmacology & Pharmacy, Vol. 2 No. 4, 2011, pp. 332-337. doi: 10.4236/pp.2011.24042.

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