Effect of genetic variation in UGT1A and ABCB1 on moxifloxacin pharmacokinetics in South African patients with tuberculosis
Loading...
Date
Authors
Naidoo, Anushka
Ramsuran, Veron
Chirehwa, Maxwell
Denti, Paolo
McIlleron, Helen
Naidoo, Kogieleum
Yende-Zuma, Nonhlanhla
Singh, Ravesh
Ngcapu, Sinaye
Chaudhry, Mamoonah
Journal Title
Journal ISSN
Volume Title
Publisher
Future Medicine
Abstract
AIM : We assessed the effect of genetic variability in UGT1A and ABCB1 genes on moxifloxacin pharmacokinetics. METHODS : Genotypes for selected UGT1A and ABCB1 SNPs were determined using a TaqMan® Genotyping OpenArray™ and high-resolution melt analysis for rs8175347. A nonlinear mixed-effects model was used to describe moxifloxacin pharmacokinetics. RESULTS : Genotypes of UGT1A SNPs, rs8175347 and rs3755319 (20.6% lower and 11.6% increased clearance, respectively) and ABCB1 SNP rs2032582 (40% reduced bioavailability in one individual) were significantly associated with changes in moxifloxacin pharmacokinetic parameters. CONCLUSION : Genetic variation in UGT1A as represented by rs8175347 to a lesser extent rs3755319 and the ABCB1 rs2032582 SNP is modestly associated with the interindividual variability reported in moxifloxacin pharmacokinetics and exposure. Clinical relevance of the effects of genetic variation on moxifloxacin pharmacokinetic requires further investigation.
Description
Keywords
Moxifloxacin, Pharmacogenetics, Pharmacokinetics, UGT1A gene, Tuberculosis (TB), Single nucleotide polymorphism, Single drug dose, Randomized controlled trial, Human immunodeficiency virus (HIV), Genotype, Genetic variability, Genetic association, Gene frequency, Drug safety, Drug exposure, Drug clearance, Drug blood level, Drug bioavailability, Drug absorption, ABCB1 gene, South African patients
Sustainable Development Goals
Citation
Naidoo, A., Ramsuran, V., Chirehwa, M. et al. 2018, 'Effect of genetic variation in UGT1A and ABCB1 on moxifloxacin pharmacokinetics in South African patients with tuberculosis', Pharmacogenomics, vol. 19, no. 1, pp 17-29.