Pharmacokinetic Drug-Drug Interactions Between Trospium Chloride and Ranitidine Substrates of Organic Cation Transporters in Healthy Human Subjects.

Pharmacokinetic Drug-Drug Interactions Between Trospium Chloride and Ranitidine Substrates of Organic Cation Transporters in Healthy Human Subjects. J Clin Pharmacol. 2019 Sep 22;: Authors: Abebe BT, Weiss M, Modess C, Tadken T, Wegner D, Meyer MJ, Schwantes U, Neumeister C, Scheuch E, Schulz HU, Tzvetkov M, Siegmund W Abstract Trospium chloride, a muscarinic receptor blocker, is poorly absorbed with different rates from areas in the jejunum and the cecum/ascending colon. To evaluate whether organic cation transporter (OCT) 1, OCT2 and multidrug and toxin extrusion (MATE) 1 and MATE2-K are involved in pharmacokinetics, competitions with ranitidine, a probe inhibitor of the cation transporters, were evaluated in transfected HEK293 cells. Furthermore, a drug interaction study with trospium chloride after intravenous (2 mg) and oral dosing (30 mg) plus ranitidine (300 mg) was performed in 12 healthy subjects and evaluated by noncompartmental analysis and population pharmacokinetic modeling. Ranitidine inhibited OCT1, OCT2, MATE1, and MATE2-K with half maximal inhibitory concentration values of 186 ± 25 µM, 482 ± 105 µM, 134 ± 37 µM, and 35 ± 11 µM, respectively. In contrast to our hypothesis, coadministration of ranitidine did not significantly decrease oral absorption of trospium. Instead, renal clearance was lowered by ∼15% (530 ± 99 vs 460 ± 120 mL/min; P < .05). It is possible that ranitidine was not ava...
Source: The Journal of Clinical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: J Clin Pharmacol Source Type: research