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Influence of CYP2B6 activity score on the pharmacokinetics and safety of single dose efavirenz in healthy volunteers

Abstract

Efavirenz is a non-nucleoside reverse transcriptase inhibitor used as first-line therapy for the treatment of HIV infection. Cytochrome P450 (CYP) CYP2B6 G516T (rs3745274) is a well-known predictor of efavirenz disposition. Dose adjustment based on G516T variant has been shown to be beneficial. However, this variant cannot explain the entire variability of efavirenz pharmacokinetics. In this study, we evaluated the influence of 11 single-nucleotide polymorphisms (SNPs) in CYP2B6, CYP2A6, CYP3A and ABCB1 (ATP-binding cassette sub-family B member 1) on the pharmacokinetics and safety of efavirenz after single oral dose administration to 47 healthy volunteers. We designed and validated a CYP2B6 activity score model based on two CYP2B6 SNPs (G516T and rs4803419) that predicted efavirenz disposition better than G516T alone.

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Funding

PZ is co-financed by Consejería de Educación, Juventud y Deporte from Comunidad de Madrid and European Social Fund.

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Contributions

PZ performed the genotyping tests. PZ, MS-R and FA-S wrote the manuscript. FA-S, DO, MR, GM and SM-V supervised and coordinated the clinical trials.

Corresponding author

Correspondence to Francisco Abad-Santos.

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Conflict of interest

FA-S and DO have been consultant or investigator in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Chemo, Cinfa, FAES, Farmalíder, Ferrer, GlaxoSmithKline, Galenicum, Gilead, Janssen-Cilag, Kern, Normon, Novartis, Servier, Silverpharma, Teva and Zambon. The other authors declare that they have no conflicts of interest.

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Zubiaur, P., Saiz-Rodríguez, M., Ochoa, D. et al. Influence of CYP2B6 activity score on the pharmacokinetics and safety of single dose efavirenz in healthy volunteers. Pharmacogenomics J 20, 235–245 (2020). https://doi.org/10.1038/s41397-019-0103-3

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