No effect of MDR1 C3435T polymorphism on oral pharmacokinetics of telmisartan in 19 healthy Chinese male subjects.
BACKGROUND
Considerable interindividual differences in both drug response and pharmacokinetics of telmisartan have been identified. This study was designed to investigate the influence of MDR1 C3435T polymorphism on pharmacokinetics of telmisartan after a single oral dose in healthy Chinese volunteers.


METHODS
A total of 61 unrelated male volunteers were genotyped for MDR1 C3435T polymorphism by using the polymerase chain reaction-restriction fragment length polymorphism method. Six 3435CC homozygotes, eight 3435CT heterozygotes, and five 3435TT homozygotes were randomly selected and received a single oral dose of 40 mg telmisartan. Plasma concentrations of telmisartan were determined by the high performance liquid chromatography-mass spectrometry method up to 48 h after telmisartan administration.


RESULTS
Interindividual variation for t(max), C(max), t(1/2), AUC(0-48), AUC(0-infinity), and clearance (CL) for telmisartan was approximately 6-, 33-, 16-, 17-, 20-, and 20-fold, respectively. C(max) (p=0.010), t(1/2) (p=0.029) and CL (p=0.010) of telmisartan were not normally distributed. MDR1 3435TT homozygotes seemed to show increases in C(max), t(max), t(1/2), AUC(0-48), and AUC(0-infinity). However, no significant differences in C(max), t(max), t(1/2), AUC(0-48), AUC(0-infinity), and CL among MDR1 C3435T genotypes were observed.


CONCLUSIONS
MDR1 C3435T polymorphism does not affect oral pharmacokinetics of telmisartan.
Guo
Xin
X
Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha, Hunan, China.
Chen
Xiao-Ping
XP
Cheng
Ze-Neng
ZN
Luo
Xi
X
Guo
Ren
R
Chen
Lei
L
Chen
Jie
J
Chen
Bo
B
Peng
Jun
J
Li
Yuan-Jian
YJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People / Q000235:genetics*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001565:Benzoates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002681:China; D002851:Chromatography, High Pressure Liquid; D005787:Gene Frequency; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D012150:Polymorphism, Restriction Fragment Length; D000077333:Telmisartan; D055815:Young Adult
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D000077333:Telmisartan