Telmisartan pharmacokinetics in Japanese renal transplant recipients.
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.
Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan.
Masatomo
M
Miura
Shigeru
S
Satoh
Kazuyuki
K
Inoue
Mitsuru
M
Saito
Tomonori
T
Habuchi
Toshio
T
Suzuki
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D044466:Asian People / Q000235:genetics; D001562:Benzimidazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001565:Benzoates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D007564:Japan; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D000077333:Telmisartan; D013997:Time Factors; D055815:Young Adult
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D014453:Glucuronosyltransferase; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D000077333:Telmisartan; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human