Renal Drug Transporters and Drug Interactions.

Details

Serval ID
serval:BIB_D25B633C64BD
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Renal Drug Transporters and Drug Interactions.
Journal
Clinical pharmacokinetics
Author(s)
Ivanyuk A., Livio F., Biollaz J., Buclin T.
ISSN
1179-1926 (Electronic)
ISSN-L
0312-5963
Publication state
Published
Issued date
08/2017
Peer-reviewed
Oui
Volume
56
Number
8
Pages
825-892
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: ppublish
Abstract
Transporters in proximal renal tubules contribute to the disposition of numerous drugs. Furthermore, the molecular mechanisms of tubular secretion have been progressively elucidated during the past decades. Organic anions tend to be secreted by the transport proteins OAT1, OAT3 and OATP4C1 on the basolateral side of tubular cells, and multidrug resistance protein (MRP) 2, MRP4, OATP1A2 and breast cancer resistance protein (BCRP) on the apical side. Organic cations are secreted by organic cation transporter (OCT) 2 on the basolateral side, and multidrug and toxic compound extrusion (MATE) proteins MATE1, MATE2/2-K, P-glycoprotein, organic cation and carnitine transporter (OCTN) 1 and OCTN2 on the apical side. Significant drug-drug interactions (DDIs) may affect any of these transporters, altering the clearance and, consequently, the efficacy and/or toxicity of substrate drugs. Interactions at the level of basolateral transporters typically decrease the clearance of the victim drug, causing higher systemic exposure. Interactions at the apical level can also lower drug clearance, but may be associated with higher renal toxicity, due to intracellular accumulation. Whereas the importance of glomerular filtration in drug disposition is largely appreciated among clinicians, DDIs involving renal transporters are less well recognized. This review summarizes current knowledge on the roles, quantitative importance and clinical relevance of these transporters in drug therapy. It proposes an approach based on substrate-inhibitor associations for predicting potential tubular-based DDIs and preventing their adverse consequences. We provide a comprehensive list of known drug interactions with renally-expressed transporters. While many of these interactions have limited clinical consequences, some involving high-risk drugs (e.g. methotrexate) definitely deserve the attention of prescribers.

Keywords
ATP Binding Cassette Transporter, Sub-Family B/drug effects, ATP Binding Cassette Transporter, Sub-Family B/metabolism, ATP Binding Cassette Transporter, Sub-Family G, Member 2/drug effects, ATP Binding Cassette Transporter, Sub-Family G, Member 2/metabolism, Animals, Biological Transport/drug effects, Biological Transport/physiology, Drug Interactions/physiology, Female, Humans, Kidney/metabolism, Kidney/ultrastructure, Kidney Tubules, Proximal/metabolism, Kidney Tubules, Proximal/secretion, Male, Multidrug Resistance-Associated Proteins/drug effects, Multidrug Resistance-Associated Proteins/metabolism, Neoplasm Proteins/drug effects, Neoplasm Proteins/metabolism, Organic Anion Transporters/drug effects, Organic Anion Transporters/metabolism, Organic Anion Transporters, Sodium-Independent/drug effects, Organic Anion Transporters, Sodium-Independent/metabolism, Organic Cation Transport Proteins/drug effects, Organic Cation Transport Proteins/metabolism, Renal Agents/metabolism, Renal Agents/pharmacokinetics, Renal Agents/therapeutic use
Pubmed
Web of science
Create date
28/02/2017 19:36
Last modification date
20/08/2019 15:52
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