Association between Sex Differences and the Pharmacokinetics of Repaglinide among a Malaysian Population英文文献资料.docVIP

Pharmacology Pharmacy, 2011, 2, 332-337 doi:10.4236/pp.2011.24042 Published Online October 2011 (http://www.SciRP.org/journal/pp) 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 1* 1 2 3 1 Department of Pharmacology, Universiti Sains Malaysia, Kota Bharu, Malaysia; 2 Department of Family Medicine, Universiti Sains Malaysia, Kota Bharu, Malaysia; laysia. * Email: tieimran@ 3 Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Ma- Received April 28 , 2011; revised May 20 , 2011; accepted June 25 , 2011. th th th 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 re- paglinide 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