LC-QQQ-MS based intracellular quantification of bictegravir in peripheral blood mononuclear cells and plasma

Jadav, Tarang; Rajput, Niraj; Sahu, Amit Kumar; Sengupta, Pinaki

doi:10.1016/j.ab.2023.115084

Cited by 3 publications

(1 citation statement)

References 28 publications

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“…However, active efflux mechanisms may also play a role, and with low unbound plasma bictegravir concentrations, saturation of efflux transporters at blood-tissues barriers cannot be assumed. While lymphoid tissues have not been studied so far, limited bictegravir accumulation into human peripheral blood mononuclear cells has been recently shown 34 . The precise contribution of ABCB1 and other efflux transporters remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Effect of ABCB1 most frequent polymorphisms on the accumulation of bictegravir in recombinant HEK293 cell lines

De Greef,

Akue,

Panin

et al. 2024

Sci Rep

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Bictegravir, a key second-generation integrase strand transfer inhibitor in the treatment of HIV, is subject to active efflux transport mediated by ABCB1 (P-glycoprotein). Several coding variants of ABCB1 have been described and associated with variable effects on substrate drugs pharmacokinetics. Here, we investigated the effect of the four most common coding ABCB1 single nucleotide polymorphisms (i.e., c.1199G > A, c.1236C > T, c.2677G > T and c.3435C > T) on the intracellular accumulation of bictegravir. Using a previously validated HEK293 recombinant cell line model, we found decreased bictegravir intracellular concentrations in cell lines overexpressing ABCB1 as compared to control cell lines, in line with the known role of ABCB1 in bictegravir transport. However, we were unable to demonstrate any significant difference in bictegravir intracellular accumulation when comparing HEK293 cells overexpressing the wild type (1236C-2677G-3435C, 1199G) or the variant (1236C-2677G-3435T, 1236T-2677T-3435T or 1199A) proteins. These findings suggest that the ABCB1 c.1199G > A and c.1236C > T-c.2677G > T-c.3435C > T variants have no or at least limited impact on the active transport of bictegravir by ABCB1.

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Section: Discussionmentioning

confidence: 99%