Publication: Differential impact of nevirapine on artemether-lumefantrine pharmacokinetics in individuals stratified by CYP2B6 c.516G>T genotypes
Issued Date
2020-01-01
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ISSN
10986596
00664804
00664804
Other identifier(s)
2-s2.0-85080090260
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Mahidol University
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SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.64, No.3 (2020)
Suggested Citation
T. Abdullahi Sa'ad, Julius O. Soyinka, Adeniyi Olagunju, Rahman A. Bolarinwa, Olusola J. Olarewaju, Moji T. Bakare-Odunola, Markus Winterberg, Joel Tarning, Andrew Owen, Saye Khoo Differential impact of nevirapine on artemether-lumefantrine pharmacokinetics in individuals stratified by CYP2B6 c.516G>T genotypes. Antimicrobial Agents and Chemotherapy. Vol.64, No.3 (2020). doi:10.1128/AAC.00947-19 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/53872
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Title
Differential impact of nevirapine on artemether-lumefantrine pharmacokinetics in individuals stratified by CYP2B6 c.516G>T genotypes
Abstract
Copyright © 2020 Abdullahi et al. There is an increased recognition of the need to identify and quantify the impact of genetic polymorphisms on drug-drug interactions. This study investigated the pharmacogenetics of the pharmacokinetic drug-drug interaction between nevirapine and artemether-lumefantrine in HIV-positive and HIV-negative adult Nigerian subjects. Thirty each of HIV-infected patients on nevirapine-based antiretroviral therapy and HIV-negative volunteers without clinical malaria, but with predetermined CYP2B6 c.516GG and TT genotypes, were administered a complete treatment dose of 3 days of artemether-lumefantrine. Rich pharmacokinetic sampling prior to and following the last dose was conducted, and the plasma concentrations of artemether/dihydroartemisinin and lumefantrine/desbutyl-lumefantrine were quantified using tandem mass spectrometry. Pharmacokinetic parameters of artemether-lumefantrine and its metabolites in HIV-infected patients on nevirapine were compared to those in the absence of nevirapine in HIV-negative volunteers. Overall, nevirapine reduced exposure to artemether and desbutyl-lumefantrine by 39 and 34%, respectively. These reductions were significantly greater in GG versus TT subjects for artemether (ratio of geometric mean [90% confidence interval]: 0.42 [0.29 to 0.61] versus 0.81 [0.51 to 1.28]) and for desbutyl-lumefantrine (0.56 [0.43 to 0.74] versus 0.75 [0.56 to 1.00]). On the contrary, it increased exposure to dihydroartemisinin and lumefantrine by 47 and 30%, respectively. These increases were significantly higher in TT versus GG subjects for dihydroartemisinin (1.67 [1.20 to 2.34] versus 1.25 [0.88 to 1.78]) and for lumefantrine (1.51 [1.20 to 1.90] versus 1.08 [0.82 to 1.42]). This study underscores the importance of incorporating pharmacogenetics into all drug-drug interaction studies with potential for genetic polymorphisms to influence drug disposition.