Organic Cation Transporter OCTs (SLC22) and MATEs (SLC47) in the Human Kidney
Journal Title: The AAPS Journal - Year 2013, Vol 15, Issue 2
Abstract
In the kidney, human organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs) are the major transporters for the secretion of cationic drugs into the urine. In the human kidney, OCT2 mediates the uptake of drugs from the blood at the basolateral membrane of tubular epithelial cells, and MATE1 and MATE2-K secrete drugs from cells into the lumen of proximal tubules. However, the expression of these transporters depends on the species of the animal. In the rodent kidney, OCT1 and OCT2 are expressed at the basolateral membrane, and MATE1 localizes at the brush-border membrane. Together, these transporters recognize various compounds and have overlapping, but somewhat different, substrate specificities. OCTs and MATEs can transport important drugs, such as metformin and cisplatin. Therefore, functional variation in OCTs and MATEs, including genetic polymorphisms or inter-individual variation, may seriously affect the pharmacokinetics and/or pharmacodynamics of cationic drugs. In this review, we summarize the recent findings and clinical importance of these transporters.
Authors and Affiliations
Hideyuki Motohashi, Ken-ichi Inui
Keywords
Related Articles
- EP ID EP681117
- DOI 10.1208/s12248-013-9465-7
- Views 48
- Downloads 0
Applications of Human Pharmacokinetic Prediction in First-in-Human Dose Estimation
Quantitative estimations of first-in-human (FIH) doses are critical for phase I clinical trials in drug development. Human pharmacokinetic (PK) prediction methods have been developed to project the human clearance (CL) a...
A survey of population analysis methods and software for complex pharmacokinetic and pharmacodynamic models with examples
An overview is provided of the present population analysis methods and an assessment of which software packages are most appropriate for various PK/PD modeling problems. Four PK/PD example problems were solved using the...
Solid Lipid Budesonide Microparticles for Controlled Release Inhalation Therapy
A solid lipid microparticle system containing budesonide was prepared by oil in water emulsification followed by spray drying. The solid lipid system was studied in terms of morphology, particle size distribution, crysta...
The composite solubility versus pH profile and its role in intestinal absorption prediction
The purpose of this study was to examine absorption of basic drugs as a function of the composite solubility curve and intestinally relevant pH by using a gastrointestinal tract (GIT) absorption simulation based on the a...
Development of an In Vivo Ovine Dry Powder Inhalation Model for the Evaluation of Conventional and Controlled Release Microparticles
Microparticles of DSCG alone or with 90% w/w PVA where prepared and characterised as described previously (5,6). Briefly, DSCG was spray dried under optimised conditions to produce a yield of microparticles with desired...