Induction effect of antiretroviral bictegravir on the expression of Abcb1, Abcg2 and Abcc1 genes associated with P-gp, Bcrp and Mrp1 transporters present in rat peripheral blood mononuclear cells.

BACKGROUND:Antiretrovirals have the potential to cause drug interactions leading to inefficacyor toxicity via activation of efflux transporters through nuclear receptors,altering drug concentrations at their target sites. RESEARCHDESIGN AND METHODS:This study used molecular dynamicsimulations and qRT-PCR to investigate bictegravir's interactions with nuclearreceptors Pxr and Car, and its effects on efflux transporters (P-gp, Bcrp,Mrp1) in rat PBMCs. PBMC/plasma drug concentrations were measured usingLC-MS/MS to assess the functional impact of transporter expression. RESULTS:Bictegravir significantly increased the expression of ABC transporters, withCar identified as a key mediator. This suggests that bictegravir's influence onnuclear receptors could affect drug transport and efficacy at the cellularlevel. CONCLUSIONS:Bictegravir activates nuclear receptors enhancing efflux transporterexpression. Understanding these interactions is crucial for preventing drug-druginteractions and reducing toxicity in clinical use. Combining Car antagonistswith bictegravir may prevent drug resistance and toxicity. However, thesefindings are based on preclinical data and necessitate further clinical trialsto confirm their applicability in clinical settings.