1. Influence of probenecid on the pharmacokinetics and pharmacodynamics of sorafenib
- Author
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Hussaarts, K.G.A.M. (Koen), Doorn, L. (Leni) van, Eechoute, K. (Karel), Damman, J. (Jeffrey), Fu, Q. (Qiang), van Doorn, N. (Nadia), Eisenmann, E.D. (Eric D.), Gibson, A.A., Hoop, E.O. (Esther Oomen-De), Bruijn, P.J. (Peter) de, Baker, S.D. (Sharyn), Koolen, S.L.W. (Stijn), Gelder, T. (Teun) van, Leeuwen, R.W.F. (Roelof) van, Mathijssen, A.H.J. (Ron), Sparreboom, A. (Alex), Bins, S. (Sander), Hussaarts, K.G.A.M. (Koen), Doorn, L. (Leni) van, Eechoute, K. (Karel), Damman, J. (Jeffrey), Fu, Q. (Qiang), van Doorn, N. (Nadia), Eisenmann, E.D. (Eric D.), Gibson, A.A., Hoop, E.O. (Esther Oomen-De), Bruijn, P.J. (Peter) de, Baker, S.D. (Sharyn), Koolen, S.L.W. (Stijn), Gelder, T. (Teun) van, Leeuwen, R.W.F. (Roelof) van, Mathijssen, A.H.J. (Ron), Sparreboom, A. (Alex), and Bins, S. (Sander)
- 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 (AUC0–12 h) as primary endpoint. During concomitant probenecid, so
- Published
- 2020
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