Jürgen Kindla1, Martin F Fromm, Jörg König. 1. Friedrich-Alexander-University Erlangen-Nuremberg, Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Clinical Pharmacology and Clinical Toxicology, Fahrstrasse 17, D-91054 Erlangen, Germany.
Abstract
BACKGROUND: Transport proteins, for example the drug export pump P-glycoprotein, are important for the absorption, distribution and excretion of drugs. Inhibition and induction of P-glycoprotein efflux function is a well-established mechanism of drug-drug interactions. Alteration of transporter-mediated drug uptake by concomitantly administered drugs may also result in a change in drug pharmacokinetics. These uptake transporter-mediated drug-drug interactions are the focus of this review. OBJECTIVE: To examine the current in vitro evidence on interactions mediated by OATPs (organic anion transporting polypeptides) and OCTs (organic cation transporters). METHODS: Comparing data of in vivo observed drug-drug interactions with in vitro analysed alterations in drug transport mediated by the hepatic expressed uptake transporters OATP1B1, OATP1B3 and OCT1 and by the renal expressed OCT2 protein. RESULTS/ CONCLUSIONS: Some of the previously in vivo described drug-drug interactions could be explained by alteration in uptake transporter function demonstrating that inhibition or induction of uptake transporters is a newly recognised mechanism of potential drug-drug interactions.
BACKGROUND: Transport proteins, for example the drug export pump P-glycoprotein, are important for the absorption, distribution and excretion of drugs. Inhibition and induction of P-glycoprotein efflux function is a well-established mechanism of drug-drug interactions. Alteration of transporter-mediated drug uptake by concomitantly administered drugs may also result in a change in drug pharmacokinetics. These uptake transporter-mediated drug-drug interactions are the focus of this review. OBJECTIVE: To examine the current in vitro evidence on interactions mediated by OATPs (organic anion transporting polypeptides) and OCTs (organic cation transporters). METHODS: Comparing data of in vivo observed drug-drug interactions with in vitro analysed alterations in drug transport mediated by the hepatic expressed uptake transporters OATP1B1, OATP1B3 and OCT1 and by the renal expressed OCT2 protein. RESULTS/ CONCLUSIONS: Some of the previously in vivo described drug-drug interactions could be explained by alteration in uptake transporter function demonstrating that inhibition or induction of uptake transporters is a newly recognised mechanism of potential drug-drug interactions.
Authors: Maria Karlgren; Gustav Ahlin; Christel A S Bergström; Richard Svensson; Johan Palm; Per Artursson Journal: Pharm Res Date: 2011-08-23 Impact factor: 4.200
Authors: Daniel Q Li; Richard Kim; Eric McArthur; Jamie L Fleet; David G Bailey; David Juurlink; Salimah Z Shariff; Tara Gomes; Muhammad Mamdani; Sonja Gandhi; Stephanie Dixon; Amit X Garg Journal: CMAJ Date: 2014-12-22 Impact factor: 8.262