PK-PD modeling of irbesartan in healthy Chinese adult volunteers under non-steady-state conditions.
The purpose of this study was to construct a pharmacokinetic/pharmacodynamic model (PK-PD model) of irbesartan in healthy Chinese adult volunteers under non-steady-state conditions and provide relevant PK/PD parameters for use in clinical practice. Thirty-six healthy Chinese adult male volunteers received 150 or 300 mg irbesartan orally in tablet form (2 groups; n = 18 per group). Plasma concentrations were determined by HPLC and pharmacological effects, including effects on systolic (SBP) and diastolic blood pressure (DBP) were measured simultaneously. The experimental data were quantitatively analyzed according to the PK-PD model construct. PK/PD parameters were calculated. Blood pressure remained almost unchanged at an irbesartan dose of 150 mg under non-steady-state conditions. After a single dose of 300 mg, the pharmacokinetic profiles of irbesartan conformed to a two-compartment model. There were hysteresis loops between drug effects and plasma concentrations. The relationship between effects and effect compartment concentrations (Ce) could be represented by the sigmoid-Emax model. The Emax values for the inhibitory effects on SBP and DBP of irbesartan were 14.8 +/- 1.5 and 9.8 +/- 2.1 mmHg respectively, the EC50 values were 0.29 +/- 0.11 and 0.18 +/- 0.07 microg x ml(-1), while the K(eo) values were 0.62 +/- 0.09 and 0.68 +/- 0.07 h(-1), respectively. The PK-PD model of irbesartan was developed in healthy Chinese adult male volunteers, and may provide a more rational basis for dosage individualization.
Huang
Xiao-Hui
XH
Center of Pharmacokinetics, College of Pharmacy, Anhui Medical University, People's Republic of China.
Li
Jun
J
Qiu
Fu-Rong
FR
Xie
Hai-Tang
HT
Huang
Ji-Han
JH
Li
Jian-Chun
JC
Zheng
Qing-Shan
QS
D000284:Administration, Oral; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D044466:Asian People; D001713:Biphenyl Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000077405:Irbesartan; D008297:Male; D008954:Models, Biological; D011237:Predictive Value of Tests; D012016:Reference Values; D013607:Tablets; D013777:Tetrazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013607:Tablets; D013777:Tetrazoles; D000077405:Irbesartan