10.5061/DRYAD.Z612JM683
Abdullahi, Sa'ad
0000-0002-6868-8687
University of Ilorin
Soyinka, Julius
Obafemi Awolowo University
Olagunju, Adeniyi
Obafemi Awolowo University
Bolarinwa, Rahman
Obafemi Awolowo University Teaching Hospitals Complex
Olarewaju, Olusola
0000-0003-0563-6932
Obafemi Awolowo University Teaching Hospitals Complex
Bakare-Odunola, Moji
University of Ilorin
Winterberg, Markus
Mahidol Oxford Tropical Medicine Research Unit
Tarning, Joel
0000-0003-4566-4030
Mahidol Oxford Tropical Medicine Research Unit
Owen, Andrew
University of Liverpool
Khoo, Saye
University of Liverpool
Differential impact of nevirapine on artemether-lumefantrine
pharmacokinetics in individuals stratified by CYP2B6 c.516G>T genotypes
Dryad
dataset
2019
HIV Research Trust
https://ror.org/00fevpc76
ELBANK029979535 to Julius O. Soyinka
Novartis (Germany)
https://ror.org/0013shd50
Capacity Development Grant to Adeniyi Olagunju and Julius O. Soyinka
2019-12-12T00:00:00Z
2019-12-12T00:00:00Z
en
https://doi.org/10.1002/jcph.1527
https://doi.org/10.1097/MJT.0000000000000340
375026 bytes
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CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
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 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 with 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
– 0.61) versus 0.81 (0.51 – 1.28)] and for desbutyl-lumefantrine [0.56
(0.43 – 0.74) versus 0.75 (0.56 – 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 – 2.34) versus 1.25 (0.88 –
1.78)] and for lumefantrine [1.51 (1.20 – 1.90) versus 1.08 (0.82 –
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.