Interplay of Breast Cancer Resistance Protein (Bcrp/Abcg2), Sex, and Fed State in Oral Pharmacokinetic Variability of Furosemide in Rats.

ABSTRACT: Poor and variable oral bioavailability of furosemide (FUR) presents critical challenges in pharmacotherapy. We investigated the interplay of breast cancer resistance protein (Bcrp)-mediated transport, sex, and fed state on FUR pharmacokinetics (PK) in rats. A crossover PK study of FUR (5 mg/kg, oral) was performed in Sprague-Dawley rats (3 males and 3 females), alone or with a Bcrp inhibitor, novobiocin (NOV) (20 mg/kg, oral), in both fed and fasted states. Co-administration of NOV significantly increased FUR extent (AUC) and rate (C_max) of exposure by more than two-fold, which indicates efficient Bcrp inhibition in the intestine. The female rats showed two-fold higher AUC and C_max, and two-fold lower renal clearance of FUR compared to the male rats. The latter was co

SUBMITTER: Sharma S 

PROVIDER: S-EPMC9968170 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature