Pharmacokinetic and pharmacodynamic of irbesartan in renal hypertensive dogs under non-steady-state and steady-state conditions.
The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of irbesartan in renal hypertensive dogs under non-steady-state and steady-state conditions using pharmacokinetic-pharmacodynamic (PK/PD) modeling. Drugs were administered intragastrically to renal hypertensive dogs, plasma drug concentration was determined by HPLC method and Pharmacologic effects, including SBP, DBP, dp/dtmax and LVSP, were measured simultaneously. AT II, Aldosterone (ALD) and Endothelin (ET) were also used as measurement of effect. The PK and PD data were quantitatively analyzed according to the PK/PD model theory. The pharmacokinetic profiles of irbesartan conformed to a two-compartment open model. There was hysteresis loops between effects and plasma concentrations under non-steady-state condition. The relationship between effects and effect compartment concentrations (Ce) could be represented by the Sigmoid-Emax model. The Hysteresis loops disappeared under steady-state condition with more rapidly attainment of maximum concentration and effect. There were certain difference of pharmacokinetic and pharmacodynamic properties between non-steady-state and steady-state condition.
Huang
Xiao-Hui
XH
College of Pharmacy, Anhui Medical University, China Yijishan Hospital, Wannan Medical College, Nanjing, China.
Qiu
Fu-Rong
FR
Xie
Hai-Tang
HT
Li
Jun
J
D047228:Angiotensin II Type 1 Receptor Blockers / Q000493:pharmacokinetics*; D000818:Animals; D001713:Biphenyl Compounds / Q000493:pharmacokinetics* / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006977:Hypertension, Renal / Q000378:metabolism*; D000077405:Irbesartan; D008297:Male; D008954:Models, Biological; D013777:Tetrazoles / Q000493:pharmacokinetics* / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000077405:Irbesartan