Effect of Hydrochlorothiazide on the Pharmacokinetics and Pharmacodynamics of the Angiotensin II Blocker Irbesartan

Abstract

The primary objective of this study was to assess the effect of hydrochlorothiazide on the pharmacokinetics of irbesartan in patients with mild-to-moderate hypertension. In addition, this study compared the pharmacodynamic and tolerability profiles of irbesartan administered both alone and in combination with hydrochlorothiazide. The study consisted of a placebo lead-in period (period A) to establish the stability of blood pressure (seated diastolic blood pressure 95 to 110mm Hg), a 7-day, single-blind treatment period (irbesartan 150mg every day) (period B), and a 7-day, double-blind treatment period [irbesartan 150mg every day plus either placebo (n = 18) or hydrochlorothiazide 25mg every day (n = 18)] (period C). Non-Black men and women 45 to 65 years of age with hypertension were included. The pharmacokinetic profile [maximum concentration of irbesartan in plasma (Cmax), time taken to reach Cmax (tmax), and the area under the plasma concentration versus time curve during a dosage interval (AUCtau)] of irbesartan was unaffected by the addition of hydrochlorothiazide. Mean changes in 24-hour AUC values for seated blood pressures from day 7 of period B to day 7 of period C were significantly lower in patients treated with irbesartan plus hydrochlorothiazide compared with those of patients treated with irbesartan plus placebo. Plasma angiotensin II levels, plasma renin activity, and urinary excretion of sodium, chloride and potassium were significantly increased, whereas urinary aldosterone and creatinine excretion remained unchanged with concomitant hydrochlorothiazide administration.