Pharmacogenetics of artemether-lumefantrine influence on nevirapine disposition: Clinically significant drug-drug interaction?
Adult
Antimalarials
/ administration & dosage
Artemether, Lumefantrine Drug Combination
/ administration & dosage
Cross-Over Studies
Cytochrome P-450 CYP2B6
/ genetics
Drug Interactions
Female
HIV Infections
/ blood
Humans
Malaria
/ complications
Male
Middle Aged
Nevirapine
/ administration & dosage
Nigeria
Polymorphism, Single Nucleotide
Reverse Transcriptase Inhibitors
/ administration & dosage
CYP2B6
artemether-lumefantrine
drug-drug interaction
nevirapine
pharmacogenetics
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
28
05
2018
revised:
29
10
2018
accepted:
08
11
2018
pubmed:
25
11
2018
medline:
8
2
2020
entrez:
25
11
2018
Statut:
ppublish
Résumé
In this study the influence of first-line antimalarial drug artemether-lumefantrine on the pharmacokinetics of the antiretroviral drug nevirapine was investigated in the context of selected single nucleotide polymorphisms (SNPs) in a cohort of adult HIV-infected Nigerian patients. This was a two-period, single sequence crossover study. In stage 1, 150 HIV-infected patients receiving nevirapine-based antiretroviral regimens were enrolled and genotyped for seven SNPs. Sparse pharmacokinetic sampling was conducted to identify SNPs independently associated with nevirapine plasma concentration. Patients were categorized as poor, intermediate and extensive metabolizers based on the numbers of alleles of significantly associated SNPs. Intensive sampling was conducted in selected patients from each group. In stage 2, patients received standard artemether-lumefantrine treatment with nevirapine, and intensive pharmacokinetic sampling was conducted on day 3. No clinically significant changes were observed in key nevirapine pharmacokinetic parameters, the 90% confidence interval for the measured changes falling completely within the 0.80-1.25 no-effect boundaries. However, the number of patients with trough plasma nevirapine concentration below the 3400 ng ml This approach highlights additional increase in the already existing risk of suboptimal trough plasma concentration, especially in extensive metabolizers when nevirapine is co-administered with artemether-lumefantrine.
Identifiants
pubmed: 30471138
doi: 10.1111/bcp.13821
pmc: PMC6379214
doi:
Substances chimiques
Antimalarials
0
Artemether, Lumefantrine Drug Combination
0
Reverse Transcriptase Inhibitors
0
Nevirapine
99DK7FVK1H
CYP2B6 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP2B6
EC 1.14.14.1
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
540-550Subventions
Organisme : Medical Research Council
ID : MR/L006758/1
Pays : United Kingdom
Informations de copyright
© 2018 The British Pharmacological Society.
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