The Effect of Gene Variants on Levonorgestrel Pharmacokinetics When Combined With Antiretroviral Therapy Containing Efavirenz or Nevirapine

Neary, M ORCID: 0000-0002-4960-2139, Lamorde, M, Olagunju, A ORCID: 0000-0002-6588-5749, Darin, KM, Merry, C, Byakika-Kibwika, P, Back, DJ, Siccardi, M ORCID: 0000-0002-3539-7867, Owen, A ORCID: 0000-0002-9819-7651 and Scarsi, KK (2017) The Effect of Gene Variants on Levonorgestrel Pharmacokinetics When Combined With Antiretroviral Therapy Containing Efavirenz or Nevirapine. CLINICAL PHARMACOLOGY & THERAPEUTICS, 102 (3). pp. 529-536.

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Abstract

Reduced levonorgestrel concentrations from the levonorgestrel contraceptive implant was previously seen when given concomitantly with efavirenz. We sought to assess whether single nucleotide polymorphisms (SNPs) in genes involved in efavirenz and nevirapine metabolism were linked to these changes in levonorgestrel concentration. SNPs in CYP2B6, CYP2A6, NR1I2, and NR1I3 were analyzed. Associations of participant demographics and genotype with levonorgestrel pharmacokinetics were evaluated in HIV-positive women using the levonorgestrel implant plus efavirenz- or nevirapine-based antiretroviral therapy (ART), in comparison to ART-naïve women using multivariate linear regression. Efavirenz group: CYP2B6 516G>T was associated with lower levonorgestrel log₁₀ C_max and log₁₀ AUC. CYP2B6 15582C>T was associated with lower log₁₀ AUC. Nevirapine group: CYP2B6 516G>T was associated with higher log₁₀ C_max and lower log₁₀ C_min . Pharmacogenetic variations influenced subdermal levonorgestrel pharmacokinetics in HIV-positive women, indicating that the magnitude of the interaction with non-nucleoside reverse transcriptase inhibitors (NNRTIs) is influenced by host genetics.

Item Type:	Article
Uncontrolled Keywords:	Humans, HIV Infections, Alkynes, Cyclopropanes, Benzoxazines, Nevirapine, Levonorgestrel, Contraceptive Agents, Female, Reverse Transcriptase Inhibitors, Multivariate Analysis, Area Under Curve, Linear Models, Prospective Studies, Pharmacogenetics, Polymorphism, Single Nucleotide, Adult, Female, Genetic Variation, Cytochrome P-450 CYP2A6, Cytochrome P-450 CYP2B6, Constitutive Androstane Receptor
Depositing User:	Symplectic Admin
Date Deposited:	05 Feb 2019 11:23
Last Modified:	19 Jan 2023 01:05
DOI:	10.1002/cpt.667
Open Access URL:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC55469...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3032280