Anushka Naidoo1, Veron Ramsuran1,2, Maxwell Chirehwa3, Paolo Denti3, Helen McIlleron3, Kogieleum Naidoo1,4, Nonhlanhla Yende-Zuma1, Ravesh Singh5, Sinaye Ngcapu1, Mamoonah Chaudhry6, Michael S Pepper6, Nesri Padayatchi1,4. 1. Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa. 2. School of Laboratory Medicine & Medical Sciences, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa. 3. Department of Medicine, Division of Clinical Pharmacology, University of Cape Town, Western Cape, South Africa. 4. MRC-CAPRISA HIV-TB Pathogenesis & Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, KwaZulu-Natal, South Africa. 5. Department of Microbiology, National Health Laboratory Services, KZN Academic Complex, Inkosi Albert Luthuli Central Hospital, Durban, KwaZulu-Natal, South Africa. 6. Department of Immunology & the Institute for Cellular & Molecular Medicine; South African Medical Research Council Extramural Unit for Stem Cell Research & Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria, Gauteng, South Africa.
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.
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 ABCB1rs2032582 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.
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