title: Modeling the heterogeneous intestinal absorption of propiverine extended-release.
abstract: Propiverine is a widely used antimuscarinic drug with bioavailability that is limited by intestinal first-pass extraction. To study the apparent heterogeneity in intestinal first-pass extraction, we performed a population analysis of oral concentration-time data measured after administration of an extended-release formulation of propiverine in ten healthy subjects. Using an inverse Gaussian function as input model, the assumption that the systemically available fraction increases as a sigmoidal function of time considerably improved the fit. The step-like increase in this fraction at time t=3.7h predicted by the model suggests that propiverine is predominantly absorbed in colon. A nearly perfect correlation was found between the estimates of bioavailability and mean dissolution time.
authors.affiliation: Department of Pharmacology, Martin Luther University Halle-Wittenberg, Germany; Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand. Electronic address: michael.weiss@medizin.uni-halle.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Weiss
authors.affiliation: Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand.
authors.forename: Pakawadee
authors.initials: P
authors.lastname: Sermsappasuk
authors.affiliation: Division of Clinical Pharmacology, Institute of Pharmacology, Ernst Moritz Arndt University, Greifswald, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Siegmund
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001561:Benzilates / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000378:metabolism*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D008954:Models, Biological; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D055815:Young Adult
chemical_list: D001561:Benzilates; D002214:Capsules; D003692:Delayed-Action Preparations; D018727:Muscarinic Antagonists; C015586:propiverine
keywords: Bioavailability; Dissolution time; Heterogenous absorption; Propiverine