Genetic variants of organic cation transporter 1 (OCT1) and OCT2 significantly reduce lamivudine uptake.

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Choi MK, Song IS

Genetic variants of organic cation transporter 1 (OCT1) and OCT2 significantly reduce lamivudine uptake.

Biopharm Drug Dispos. 2012 Apr;33(3):170-8. doi: 10.1002/bdd.1783. Epub 2012 Mar 17.

PubMed ID
22415520 [ View in PubMed
]
Abstract

The study sought to investigate the effect of genetic variants of OCT1 (OCT1-P283L and -P341L) and OCT2 (OCT2-T199I, -T201M and -A270S), which were identified in a Korean population, on the transport of lamivudine in vitro and to compare the substrate dependent effects of OCT1 and OCT2 variants with 1-methyl-4-phenylpyridinium (MPP+), tetraethyl ammonium (TEA), metformin and lamivudine as substrates for these transporters. When the transport kinetics of lamivudine uptake in oocytes overexpressing OCT1 and OCT2 wild-type (WT) and variant proteins were measured, lamivudine uptake mediated by OCT1-WT was saturable, and uptake was decreased in oocytes expressing OCT1-P283L and -P341L variants compared with that in OCT1-WT. The Clint of lamivudine in oocytes expressing OCT1-P283L was decreased by 85.1% compared with OCT1-WT, whereas it was decreased by 48.7% in oocytes expressing OCT1-P341L. The Clint of lamivudine in oocytes expressing OCT2-T199I, -T201M and -A270S was decreased by 86.2%, 88.9% and 73.6%, respectively, compared with OCT2-WT. When comparing various substrates such as MPP+, TEA, metformin and lamivudine, the effects of the OCT1 genetic polymorphisms on their uptake were not identical. However, contrary to the case of OCT1, the uptake of MPP+, TEA, metformin and lamivudine in oocytes expressing OCT2-T199I, -T201M and -A270S variants was decreased significantly compared with that in oocytes expressing OCT2-WT. In conclusion, the effect of genetic variations of OCT1 and OCT2 on the uptake of MPP+, TEA, metformin and lamivudine was substrate-dependent.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
LamivudineSolute carrier family 22 member 1ProteinHumans
Unknown
Substrate
Details