Intracellular drug bioavailability: a new predictor of system dependent drug disposition.

ABSTRACT: Intracellular drug exposure is influenced by cell- and tissue-dependent expression of drug-transporting proteins and metabolizing enzymes. Here, we introduce the concept of intracellular bioavailability (F_ic) as the fraction of extracellular drug available to bind intracellular targets, and we assess how F_ic is affected by cellular drug disposition processes. We first investigated the impact of two essential drug transporters separately, one influx transporter (OATP1B1; SLCO1B1) and one efflux transporter (P-gp; ABCB1), in cells overexpressing these proteins. We showed that OATP1B1 increased F_ic of its substrates, while P-gp decreased F_ic. We then investigated the impact of the concerted action of multiple transporters and metabolizing enzymes in

SUBMITTER: Mateus A 

PROVIDER: S-EPMC5320532 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature