Journal
CLINICA CHIMICA ACTA
Volume 399, Issue 1-2, Pages 83-87Publisher
ELSEVIER
DOI: 10.1016/j.cca.2008.09.020
Keywords
Telmisartan; UCT; OATP; MRP2; Pharmacokinetics
Categories
Funding
- Japan Society for the Promotion of Science, Tokyo, Japan [19923020, 20591894]
- Novartis Tokyo, Japan
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Background: Telmisartan is taken up into human hepatocytes by organic anion-transporting polypeptide (OATP/ gene SLCO) and is glucuronized by uridine diphosphate-glucuronosyltransferases (UGTs) into the acylglucuronide, and it is then excreted by transporters such as multidrug resistance 1 (MDR1/gene ABCB1), multidrug resistance protein 2 (MRP2/gene ABCC2), or breast cancer resistance protein (BCRP/gene ABCG2). We elucidated the association of UGTs (1A1, 1A6, 1A7, 1A9 and 2B7), SLCOs (1B1, 1B3 and 2B1), ABCB1, ABCC2 and ABCG2 polymorphisms with steady-state telmisartan pharmacokinetics in 12 Japanese renal transplant recipients. Methods: Recipients were given 40 mg of telmisartan for at least 6 months. Blood was sampled 1 y after transplantation. Plasma concentrations of telmisartan were measured by HPLC. Results: In subjects with the ABCC2 -24C/T genotype, the maximum plasma concentration of telmisartan was significantly greater than that in C/C genotype (96.8 vs.57.4 ng/ml, respectively, P=0.0094). In ABCC2-24C/C, the second peak plasma concentration of telmisartan was observed 13 h after oral administration, but not ABCC2 -24C/T genotype group. There was no significant difference in the telmisartan pharmacokinetics between genotype groups of other transporters such as SLCO1B3, ABCB1 and ABCG2 or UGTs. Conclusions: ABCC2 genetic polymorphisms appear to strongly influence inter-individual variation of telmisartan pharmacokinetics. MRP2 may be predominantly involved in the telmisartan pharmacokinetics in humans. (C) 2008 Elsevier B.V. All rights reserved.
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