Pharmacodynamics and pharmacokinetics of irbesartan in patients with mild to moderate hypertension

Abstract

Background: The pharmacodynamics (plasma angiotensin II [AII], plasma renin activity [PRA], renal function, blood pressure [BP], urinary excretion of major metabolites of prostacyclin [PGI2-M], and thromboxane A2 [TXA2- M]) and pharmacokinetics of irbesartan were assessed in hypertensive patients. Methods and Results: Twenty-four white patients with seated diastolic blood pressure 95 to 110 mmHg were randomized to double-blind irbesartan 300 mg or placebo once daily for 4 weeks, following a placebo lead-in. Irbesartan-treated patients had significantly greater 24hour area under the curve values for mean change from baseline in AII and PRA versus placebo-treated patients on day B15 (AII [pg·h/mL]: 261 ± 515 vs 12 ± 51; PRA [(ng/mL/h)·h]: 74 ± 162 vs -2 ± 14; P values < .05). Pharmacokinetics were comparable to those from previous studies. The hourly relationship between plasma irbesartan concentration and antihypertensive effect indicated a broad, clockwise hysteresis, with peak concentration occurring at 1.5 hours, whereas peak antihypertensive effect occurred at 4 hours. Conclusions: Irbesartan increases plasma AII and PRA and lowers BP consistent with AT1 receptor blockade, without clinically important effects on renal function.