The effect of gender and ABCB1 gene polymorphism on the pharmacokinetics of azithromycin in healthy male and female Pakistani subjects
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY(2020)
摘要
In the current study, the possible outcome of gender difference and genotypic polymorphism of the ABCB1 gene encoding P-glycoprotein on the pharmacokinetics of azithromycin has been evaluated. An open-label, comparative pharmacokinetic study was done in healthy Pakistani volunteers (females (n = 8) and males (n = 8)). They were administered a single 500 mg oral dose of azithromycin. Blood samples (approximate to 5 mL) were collected in heparinized tubes and the HPLC/MS/MS method was used to determine azithromycin plasma levels. ABCB1 polymorphism (single nucleotide polymorphisms) at C3435T, G26SST was performed using the RFLP-PCR method. The Student t test was applied to compare pharmacokinetic parameters of azithromycin between male and female human subjects (at 95% CI) using GraphPad Prism-8. A significant difference was observed in pharmacokinetic parameters between males and females, as C-max in males (230 +/- 80.2 ng/mL) was significantly higher than in females (224.9 +/- 75.5 ng/mL), while (AUC)(0)(t )was also significantly higher (p < 0.05) in males (2102 +/- 200.3 ng.h(-1).mL(-1)) compared to females (1825.7 +/- 225.4 ng.h(-1).mL(-1)). There was a significant variation in C(max )and AUC in three ABCBl genotyping groups as well. Gender difference and ABCB1 gene polymorphisms have a significant impact on the pharmacokinetics of azithromycin, as they contribute to interindividual variability in therapeutic response.
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关键词
gene polymorphism,pharmacokinetics,gender differences,ABCB1
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