title: Drug disposition before and after gastric bypass: fenofibrate and posaconazole.
abstract: 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.
  
  
  
  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 (AUC0-48 h), the peak plasma concentration (Cmax)and the time to reach peak concentration (Tmax).
  
  
  
  After administration of fenofibrate, no relevant differences in AUC0-48 h, Cmaxand Tmaxbetween the pre- and postoperative setting were observed. The geometric mean of the ratio of AUC0-48 hpost/pre-RYGB for fenofibrate was 1.10 [95% confidence interval (CI) 0.87, 1.40; P = 0.40]. For posaconazole, an important decrease in AUC0-48 hand Cmaxfollowing RYGB was shown; the geometric mean of the AUC0-48 hpost/pre-RYGB ratio was 0.68 (95% CI 0.48, 0.96; P = 0.03) and the geometric mean of the Cmaxpre/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 Tmaxwas observed.
  
  
  
  The disposition of fenofibrate was not altered after RYGB, whereas the oral disposition of posaconazole was significantly decreased following RYGB.
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.|Clinical and Experimental Endocrinology, KU Leuven and Department of Endocrinology, University Hospitals Leuven/KU Leuven, Leuven, Belgium.
authors.forename: Ina
authors.initials: I
authors.lastname: Gesquiere
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Hens
authors.affiliation: Clinical and Experimental Endocrinology, KU Leuven and Department of Endocrinology, University Hospitals Leuven/KU Leuven, Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Van der Schueren
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Raf
authors.initials: R
authors.lastname: Mols
authors.affiliation: Center for Clinical Pharmacology, University Hospitals Leuven/KU Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: de Hoon
authors.affiliation: Clinical and Experimental Endocrinology, KU Leuven and Department of Endocrinology, University Hospitals Leuven/KU Leuven, Leuven, Belgium.|Department of Abdominal Surgery, KU Leuven/University Hospitals Leuven, Leuven, Belgium.
authors.forename: Matthias
authors.initials: M
authors.lastname: Lannoo
authors.affiliation: Clinical and Experimental Endocrinology, KU Leuven and Department of Endocrinology, University Hospitals Leuven/KU Leuven, Leuven, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Matthys
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Foulon
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium. patrick.augustijns@pharm.kuleuven.be.
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
mesh_terms: D000284:Administration, Oral; D019540:Area Under Curve; D011345:Fenofibrate / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015390:Gastric Bypass; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D014230:Triazoles; C101425:posaconazole; D011345:Fenofibrate
keywords: Roux-en-Y gastric bypass; absorption; bariatric surgery; fenofibrate; pharmacokinetics; posaconazole