Effect of four ABCB1 genetic polymorphisms on the accumulation of darunavir in HEK293 recombinant cell lines

Autor: Nadtha Panin, Gabriel Stillemans, Halima El-Hamdaoui, Laure Elens, Kévin-Alexandre Delongie, Happy Phanio Djokoto, Vincent Haufroid
Přispěvatelé: UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - SSS/IREC/LTAP - Louvain Centre for Toxicology and Applied Pharmacology, UCL - (SLuc) Service de biochimie médicale
Rok vydání: 2021
Předmět:
Zdroj: Scientific Reports, Vol. 11, no. 1, p. 9000 [1-7] (2021)
Scientific Reports
Scientific Reports, Vol 11, Iss 1, Pp 1-7 (2021)
ISSN: 2045-2322
Popis: The intracellular penetration of darunavir, a second-generation HIV protease inhibitor, is limited by the activity of the efflux P-glycoprotein (ABCB1). ABCB1 expression and/or activity levels can vary between individuals due to genetic polymorphisms including the c.1199G>A, c.1236C>T, c.2677G>T and c.3435C>T variants, which could in part explain why the pharmacokinetics of darunavir are so variable from one individual to another. While a few clinical studies have failed to demonstrate an influence of these polymorphisms on darunavir pharmacokinetics, drug-drug interactions and methodological limitations may have prevented them from revealing the true influence of ABCB1 variants. In this work, we report on the intracellular accumulation of darunavir in recombinant HEK293 cell lines expressing wild-type ABCB1 or one of several variants: ABCB1 1199A, ABCB1 3435T, and ABCB1 1236T/2677T/3435T. We demonstrate that while ABCB1 expression limits intracellular accumulation of darunavir, there is no significant difference in efflux activity between cells expressing wild-type ABCB1 and those that express any of the studied variants.
Databáze: OpenAIRE
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