title: Trospium chloride is absorbed from two intestinal "absorption windows" with different permeability in healthy subjects.
abstract: Intestinal P-glycoprotein is regio-selectively expressed and is a high affinity, low capacity efflux carrier for the cationic, poorly permeable trospium. Organic cation transporter 1 (OCT1) provides lower affinity but higher capacity for trospium uptake. To evaluate regional intestinal permeability, absorption profiles after gastric infusion of trospium chloride (30mg/250ml=[I]2) for 6h and after swallowing 30mg immediate-release tablets in fasted and fed healthy subjects, were evaluated using an inverse Gaussian density function to model input rate and mean absorption time (MAT). Trospium chloride was slowly absorbed (MAT ∼10h) after gastric infusion involving two processes with different input rates, peaking at about 3h and 7h. Input rates and MAT were influenced by dosage form and meal. In conclusion, trospium is absorbed from two "windows" located in the jejunum and cecum/ascending colon, whose uptake capacity might result from local abundance and functional interplay of P-glycoprotein and OCT1.
authors.affiliation: Department of Clinical Pharmacology, Center of Drug Absorption and Transport, University Medicine of Greifswald, Greifswald, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Tadken
authors.affiliation: Department of Pharmacology, Martin Luther University Halle-Wittenberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Weiss
authors.affiliation: Department of Clinical Pharmacology, Center of Drug Absorption and Transport, University Medicine of Greifswald, Greifswald, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Modess
authors.affiliation: Department of Clinical Pharmacology, Center of Drug Absorption and Transport, University Medicine of Greifswald, Greifswald, Germany.
authors.forename: Danilo
authors.initials: D
authors.lastname: Wegner
authors.affiliation: Department of Clinical Pharmacology, Center of Drug Absorption and Transport, University Medicine of Greifswald, Greifswald, Germany.
authors.forename: Tarek
authors.initials: T
authors.lastname: Roustom
authors.affiliation: Department Medical Science/Clinical Research, Dr. R. Pfleger GmbH, Bamberg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Neumeister
authors.affiliation: Department Medical Science/Clinical Research, Dr. R. Pfleger GmbH, Bamberg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schwantes
authors.affiliation: Laboratory for Contract Research in Clinical Pharmacology and Biopharmaceutical Analytics, Bad Schwartau, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Schulz
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Center of Drug Absorption and Transport, University of Greifswald, Greifswald, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Weitschies
authors.affiliation: Department of Clinical Pharmacology, Center of Drug Absorption and Transport, University Medicine of Greifswald, Greifswald, Germany. Electronic address: werner.siegmund@uni-greifswald.de.
authors.forename: Werner
authors.initials: W
authors.lastname: Siegmund
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000328:Adult; D001561:Benzilates / Q000378:metabolism*; D002432:Cecum / Q000378:metabolism*; D044682:Colon, Ascending / Q000378:metabolism*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D009662:Nortropanes / Q000378:metabolism*; D027702:Organic Cation Transporter 1 / Q000378:metabolism; D010539:Permeability; D013607:Tablets / Q000378:metabolism; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001561:Benzilates; D009662:Nortropanes; D027702:Organic Cation Transporter 1; D013607:Tablets; C003330:trospium chloride
keywords: Food effects; Gastric infusion; OCT1; P-glycoprotein; Pharmacokinetics; Trospium chloride