Telmisartan pharmacokinetics in Japanese renal transplant recipients.

Abstract

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.

• Authors: Masatomo Miura, Shigeru Satoh, Kazuyuki Inoue, Mitsuru Saito, Tomonori Habuchi, Toshio Suzuki
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 399 Issue 1-2 Pg. 83-7 (Jan 2009) ISSN: 1873-3492 [Electronic] Netherlands
• PMID: 18838068 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCB1 protein, human
• ABCC2 protein, human
• ABCG2 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters
• Angiotensin-Converting Enzyme Inhibitors
• Benzimidazoles
• Benzoates
• Multidrug Resistance-Associated Protein 2
• Multidrug Resistance-Associated Proteins
• Neoplasm Proteins
• Glucuronosyltransferase
• Telmisartan

Topics

• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters (genetics)
• Adult
• Angiotensin-Converting Enzyme Inhibitors (administration & dosage, blood, pharmacokinetics)
• Asian People (genetics)
• Benzimidazoles (administration & dosage, blood, pharmacokinetics)
• Benzoates (administration & dosage, blood, pharmacokinetics)
• Chromatography, High Pressure Liquid
• Female
• Genotype
• Glucuronosyltransferase (genetics)
• Humans
• Japan
• Kidney Transplantation
• Male
• Middle Aged
• Multidrug Resistance-Associated Protein 2
• Multidrug Resistance-Associated Proteins (genetics)
• Neoplasm Proteins (genetics)
• Polymorphism, Genetic (genetics)
• Telmisartan
• Time Factors
• Young Adult