The purpose of the study is: - to determine absolute bioavailability, input rates, distribution volume, renal and intestinal excretion of trospium in subjects with wild-type of SLC22A1 rs72552763 and rs12208357 and in subjects with homozygous variant alleles of SLC22A1 rs72552763 or rs12208357 - to determine absolute bioavailability, input rates, distribution volume and renal and intestinal excretion of trospium in subjects with wild-type alleles of SLC22A1 rs72552763 and rs12208357 after co-medication of 300 mg of the OCT1- inhibitor ranitidine - to determine absolute bioavailability, input rates, distribution volume and renal and intestinal excretion of trospium in subjects with wild-type alleles of SLC22A1 rs72552763 and rs12208357 after co-medication of 500 mg of the P-glycoprotein- inhibitor clarithromycin - to determine absolute bioavailability, input rates, distribution volume and renal and intestinal excretion of trospium in subjects with homozygous variant alleles of SLC22A1 rs72552763 or rs12208357 after co-medication of 500 mg of the P-glycoprotein- inhibitor clarithromycin.

NCT03011463

Conditions

1. Pharmacokinetics
2. Inhibition Enzyme
3. Drug Interaction Potentiation

Interventions

1. Drug: intravenous infusion of 2 mg trospium chloride
2. Drug: oral administration of 30 mg trospium chloride
3. Drug: oral administration of 300 mg ranitidine
4. Drug: oral administration of 500 mg clarithromycin

Pharmacokinetic Interaction Between Trospium With an Inhibitor of OCT1 and of P-gp in Subjects Genotyped for OCT1 The purpose of the study is: - to determine absolute bioavailability, input rates, distribution volume, renal and intestinal excretion of trospium in subjects with wild-type of SLC22A1 rs72552763 and rs12208357 and in subjects with homozygous variant alleles of SLC22A1 rs72552763 or rs12208357 - to determine absolute bioavailability, input rates, distribution volume and renal and intestinal excretion of trospium in subjects with wild-type alleles of SLC22A1 rs72552763 and rs12208357 after co-medication of 300 mg of the OCT1- inhibitor ranitidine - to determine absolute bioavailability, input rates, distribution volume and renal and intestinal excretion of trospium in subjects with wild-type alleles of SLC22A1 rs72552763 and rs12208357 after co-medication of 500 mg of the P-glycoprotein- inhibitor clarithromycin - to determine absolute bioavailability, input rates, distribution volume and renal and intestinal excretion of trospium in subjects with homozygous variant alleles of SLC22A1 rs72552763 or rs12208357 after co-medication of 500 mg of the P-glycoprotein- inhibitor clarithromycin.

Inclusion Criteria: - ethnic origin: Caucasian - genotypes of OCT1: wild-type and homozygous variant alleles of SLC22A1 rs72552763 or rs12208357.

laxatives, metoclopramide, loperamide, antacids, H2-receptor antagonists, proton pump inhibitors, anticholinergics) - any other medication within two weeks prior to the first administration of the study medication, but at least 10-time the half-live of the respective drug (except oral contraceptives) - intake of grapefruit or orange containing food or beverages within 14 days prior to administration of the study medication - intake of poppy seed containing food or beverages within 14 days prior to administration of the study medication - known allergic reactions to the active ingredients used, other H2-receptor antagonists, macrolide antibiotics or to constituents of the study medication Inclusion Criteria: - ethnic origin: Caucasian - genotypes of OCT1: wild-type and homozygous variant alleles of SLC22A1 rs72552763 or rs12208357.