Pharmacokinetics of telmisartan in healthy Chinese subjects after oral administration of two dosage levels.
To study the pharmacolkinetics of telmisartan in healthy Chinese male subjects after oral administration of two dosage levels, 36 healthy subjects were divided into two groups and given a single oral dose of 40 or 80 mg telmisartan (CAS 144701-48-4, MicardisPlus). A sensitive liquid chromatography-tandem mass spectrometry method (LC-MS-MS) was used for the determination of telmisartan in plasma. Both, a non-compartmental and compartmental method were used for analysis of parameters of kinetics. The main pharmacokinetic parameters of the 40 mg and 80 mg regimen group were as follows: t(max) (1.76 +/- 1.75) h, (1.56 +/- 1.09) h, C(max) (163.2 +/- 128.4) ng/mL, (905.7 +/- 583.4) ng/mL, t1/2 (23.6 +/- 10.8) h, (23.0 +/- 6.4) h, AUC(o-t) (1456 +/- 1072) ng x h/mL, (6759 +/- 3754) ng x h/mL, AUC(o-infinity (1611 +/- 1180) ng x h/mL, (7588 +/- 4661) ng x h/mL, respectively. After dose normalization, there was significant difference for main pharmacokinetic parameters C(max) AUC(o-t) and AUC(o-infinity) between two dosage level groups. The plasma concentration-time profile of telmisartan was characterized by a high degree of inter-individual variability and the disposition of telmisartan in healthy Chinese subjects was dose-dependent. The pharmacokinetic parameters C(max) and AUC(o-inifinity) of the 80 mg regimen group increased to about 5-fold compared to that of the 40 mg regimen group, but there was no significant difference for t(max) and t1/2 between the two dose groups.
Zhang
Peng
P
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
Zhang
Yifan
Y
Chen
Xiaoyan
X
Li
Rongqin
R
Yin
Jian
J
Zhong
Dafang
D
D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; 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; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D000077333:Telmisartan
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D000077333:Telmisartan