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Renal Drug Transporters and Drug Interactions
- Source :
- Clinical pharmacokinetics. 56(8)
- Publication Year :
- 2017
-
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.
- Subjects :
- Drug
Male
ATP Binding Cassette Transporter, Subfamily B
Organic anion transporter 1
Abcg2
Organic Cation Transport Proteins
media_common.quotation_subject
OATP4C1
Organic Anion Transporters
ATP-binding cassette transporter
Pharmacology
Organic Anion Transporters, Sodium-Independent
Kidney
Renal Agents
030226 pharmacology & pharmacy
Kidney Tubules, Proximal
03 medical and health sciences
0302 clinical medicine
ATP Binding Cassette Transporter, Subfamily G, Member 2
Animals
Humans
Pharmacology (medical)
Drug Interactions
media_common
Organic cation transport proteins
biology
Chemistry
Kidney metabolism
Transporter
Biological Transport
Multidrug Resistance-Associated Protein 2
Neoplasm Proteins
030220 oncology & carcinogenesis
biology.protein
Female
Multidrug Resistance-Associated Proteins
Subjects
Details
- ISSN :
- 11791926
- Volume :
- 56
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Clinical pharmacokinetics
- Accession number :
- edsair.doi.dedup.....b93c22fd18f52d72a3e13c5db79bdc39