原创力文档association between sex differences and the pharmacokinetics of repaglinide among a malaysian population性别差异之间的关联、repaglinide在马来西亚人口的药物动力学.pdfVIP
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association between sex differences and the pharmacokinetics of repaglinide among a malaysian population性别差异之间的关联、repaglinide在马来西亚人口的药物动力学
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
1* 1 2 3
Ruzilawati Abu Bakar , Mohd Suhaimi Ab Wahab , Imran Ahmad , Gan Siew Hua
1Department of Pharmacology, Universiti Sains Malaysia, Kota Bharu, Malaysia; 2Department of Family Medicine, Universiti Sains
Malaysia, Kota Bharu, Malaysia; 3Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Ma-
laysia.
*
Email: tieimran@
Received April 28th, 2011; revised May 20th, 2011; accepted June 25th, 2011.
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 CYP 3A4*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 betw een 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 = 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) hig
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