Distribution of ABCB1 Genetic Variants and their Association with Moxifloxacin Pharmacokinetics in Hospitalized Patients with Acute Exacerbation of COPD
Abstract
Abstract Interindividual variability in moxifloxacin pharmacokinetics may contribute to differences in therapeutic response and has been partially attributed to genetic factors affecting drug transport. The present study investigated the distribution of three common ABCB1 polymorphisms, c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642), and explored their association with moxifloxacin pharmacokinetics in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Thirty adult patients receiving intravenous moxifloxacin 400 mg once daily were included. Plasma concentrations were quantified using a validated HPLC–UV method, and individual pharmacokinetic parameters were obtained from a previously developed population pharmacokinetic model. Genotyping was performed using TaqMan SNP Genotyping Assays. Genotype, allele and haplotype frequencies were compared with previously published data from a healthy Macedonian population. The observed genotype and allele frequencies were comparable to those reported in healthy individuals. Minor allele frequencies were 43.3% for c.1236C>T, 41.6% for c.2677G>T/A, and 45.0% for c.3435C>T. Two predominant haplotypes were identified: CGC (56.7%) and TTT (43.3%). Differences in moxifloxacin exposure were observed between genotype groups. For c.1236C>T, heterozygous carriers demonstrated the highest mean exposure, with a mean AUC of 56.24 mg·h/L and the lowest CL (9.55 L/h), whereas…
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