Abstract
In the current study, the possible outcome of sex difference and genotypic polymorphism of ABCB1 gene encoding p-glycoprotein (involved in biliary excretion of azithromycin) on the pharmacokinetics of azithromycin has been evaluated.
An open-label, the comparative pharmacokinetic study was arranged by including female and male healthy Pakistani volunteers. They were administered with a single oral dose of azithromycin 500 mg. The blood samples (≈ 5 ml) were collected in heparinized tubes and HPLC/MS/MS method was used to determine azithromycin plasma levels. Student t-test was applied to compare pharmacokinetic parameters of azithromycin between male and female human subjects (at 95% CI) using Graph Pad prism8.
A significant difference was observed in PK parameters between males and females as Cmax in males (230 ±80.2 ng/ml) was significantly higher than females (224.9 ± 75.5 ng/ml), while was also significantly higher (p < 0.05) in males (2102 ± 200.3ng.hr/ml ) compared with females (1825.7 ± 225.4 ng.hr/ml). There was a significant variation in Cmax and AUC in three ABCB1 genotyping groups as well.
Gender difference and ABCB1 gene (encoding P-glycoprotein) polymorphisms have a significant impact on the pharmacokinetics of azithromycin as they contribute to inter-individual variability in therapeutic response.