PHARMACOKINETICS Drug disposition before and after gastric bypass: fenofibrate and posaconazole Correspondence Professor Patrick Augustijns, PharmD-PhD, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, O&N2, Herestraat 49, Box 921, 3000 Leuven, Belgium. Tel.: + 32 1633 0301; Fax: + 32 1633 0305; E-mail: patrick.augustijns@pharm.kuleuven.be Received 15 March 2016; revised 24 May 2016; accepted 22 June 2016 Ina Gesquiere 1,2 , Bart Hens 1 , Bart Van der Schueren 2 , Raf Mols 1 , Jan de Hoon 3 , Matthias Lannoo 2,4 , Christophe Matthys 2 , Veerle Foulon 1 and Patrick Augustijns 1 1 Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium, 2 Clinical and Experimental Endocrinology, KU Leuven and Department of Endocrinology, University Hospitals Leuven/KU Leuven, Leuven, Belgium, 3 Center for Clinical Pharmacology, University Hospitals Leuven/KU Leuven, Leuven, Belgium, and 4 Department of Abdominal Surgery, KU Leuven/University Hospitals Leuven, Leuven, Belgium Keywords absorption, bariatric surgery, fenofibrate, pharmacokinetics, posaconazole, Roux-en-Y gastric bypass AIMS Roux-en-Y gastric bypass (RYGB) alters the anatomical structure of the gastrointestinal tract, which can result in alterations in drug disposition. The aim of the present study was to evaluate the oral disposition of two compounds belonging to the Biopharmaceutical Classification System Class II – fenofibrate (bile salt-dependent solubility) and posaconazole (gastric pH-dependent dissolution) – before and after RYGB in the same individuals. METHODS A single-dose pharmacokinetic study with two model compounds – namely, 67 mg fenofibrate (Lipanthyl®) and 400 mg posaconazole (Noxafil®) – was performed in 12 volunteers pre- and post-RYGB. After oral administration, blood samples were collected at different time points up to 48 h after administration. Plasma concentrations were determined by high-performance liquid chromatography in order to calculate the area under the concentration–time curve up to 48 h (AUC 0–48 h ), the peak plasma concentration (C max) and the time to reach peak concentration (T max ). RESULTS After administration of fenofibrate, no relevant differences in AUC 0–48 h ,C max and T max between the pre- and postoperative setting were observed. The geometric mean of the ratio of AUC 0–48 h post/pre-RYGB for fenofibrate was 1.10 [95% confidence interval (CI) 0.87, 1.40; P = 0.40]. For posaconazole, an important decrease in AUC 0–48 h and C max following RYGB was shown; the geometric mean of the AUC 0–48 h post/pre-RYGB ratio was 0.68 (95% CI 0.48, 0.96; P = 0.03) and the geometric mean of the C max pre/post-RYGB ratio was 0.60 (95% CI 0.39, 0.94; P = 0.03). The decreased exposure of posaconazole could be explained by the increased gastric pH and accelerated gastric emptying of fluids post-RYGB. No difference for T max was observed. CONCLUSIONS The disposition of fenofibrate was not altered after RYGB, whereas the oral disposition of posaconazole was significantly decreased following RYGB. British Journal of Clinical Pharmacology Br J Clin Pharmacol (2016) 82 1325–1332 1325 © 2016 The British Pharmacological Society DOI:10.1111/bcp.13054