The Effect of Gene Variants on Levonorgestrel Pharmacokinetics when Combined with Antiretroviral Therapy containing Efavirenz or Nevirapine

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dc.contributor.authorNeary, Megan
dc.contributor.authorLamorde, Mohammed
dc.contributor.authorOlagunju, Adeniyi
dc.contributor.authorDarin, Kristin M.
dc.contributor.authorMerry, Concepta
dc.contributor.authorByakika-Kibwika, Pauline
dc.contributor.authorBack, David J.
dc.contributor.authorSiccardi, Marco
dc.contributor.authorOwen, Andrew
dc.contributor.authorScarsi, Kimberly K.
dc.date.accessioned2022-01-13T17:24:27Z
dc.date.available2022-01-13T17:24:27Z
dc.date.issued2017
dc.description.abstractReduced 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 analysed. Associations of participant demographics and genotype with levonorgestrel pharmacokinetics were evaluated in HIV-positive women using the levonorgestrel implant plus efavirenz- or nevirapine-based ART, in comparison to ART-naïve women using multivariate linear regression. Efavirenz group: CYP2B6 516G>T was associated with lower levonorgestrel log10 Cmax and log10 AUC. CYP2B6 15582C>T was associated with lower log10 AUC. Nevirapine group: CYP2B6 516G>T was associated with higher log10 Cmax and lower log10 Cmin. 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.en_US
dc.identifier.citationNeary, M., Lamorde, M., Olagunju, A., Darin, K. M., Merry, C., Byakika‐Kibwika, P., ... & Scarsi, K. K. (2017). The effect of gene variants on levonorgestrel pharmacokinetics when combined with antiretroviral therapy containing efavirenz or nevirapine. Clinical Pharmacology & Therapeutics, 102(3), 529-536. doi:10.1002/cpt.667.en_US
dc.identifier.other10.1002/cpt.667.
dc.identifier.urihttps://nru.uncst.go.ug/xmlui/handle/123456789/1270
dc.language.isoenen_US
dc.publisherClinical Pharmacology & Therapeuticsen_US
dc.subjectLevonorgestrelen_US
dc.subjectEfavirenzen_US
dc.subjectNevirapineen_US
dc.subjectPharmacokineticsen_US
dc.subjectPharmacogeneticsen_US
dc.subjectHIVen_US
dc.subjectCYP2A6en_US
dc.subjectCYP2B6en_US
dc.subjectNR1I2en_US
dc.subjectNR1I3en_US
dc.subjectSingle nucleotide polymorphismsen_US
dc.titleThe Effect of Gene Variants on Levonorgestrel Pharmacokinetics when Combined with Antiretroviral Therapy containing Efavirenz or Nevirapineen_US
dc.typeArticleen_US
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