Influence of Probenecid on the Pharmacokinetics and Pharmacodynamics of Sorafenib.

ABSTRACT: Prior studies have demonstrated an organic anion transporter 6 (OAT6)-mediated accumulation of sorafenib in keratinocytes. The OAT6 inhibitor probenecid decreases sorafenib uptake in skin and might, therefore, decrease sorafenib-induced cutaneous adverse events. Here, the influence of probenecid on sorafenib pharmacokinetics and toxicity was investigated. Pharmacokinetic sampling was performed in 16 patients on steady-state sorafenib treatment at days 1 and 15 of the study. Patients received sorafenib (200-800 mg daily) in combination with probenecid (500 mg two times daily (b.i.d.)) on days 2-15. This study was designed to determine bioequivalence with geometric mean Area under the curve from zero to twelve hours (AUC_{0-12 h}) as primary endpoint. During concomitant probenecid, s

SUBMITTER: Hussaarts KGAM 

PROVIDER: S-EPMC7559746 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature