Pharmacokinetics,safety, and antihypertensive efficacy of losartan in combination with hydrochlorothiazide in hypertensive patients with renal impairment

The pharmacokinetics and pharmacodynamics of 7 days of treatment with losartan 50 mg/hydrochlorothiazide 12.5 mg were evaluated in 14 patients with normal renal function and in 12 patients with mild to moderate renal impairment. The efficacy of losartan 50 mg/hydrochlorothiazide 12.5 mg titrated to losartan 100 mg/hydrochlorothiazide 25 mg was examined in 32 hypertensive patients with mild to moderate renal impairment who were treated for 12 weeks. Safety was assessed in both studies by the incidence of adverse experiences. After 7 days of treatment, the AUC for losartan, E-3174, and hydrochlorothiazide was slightly higher in patients with mild to moderate renal impairment, but the reduction in blood pressure (BP) after 7 days was not different between the two groups. The final (week 12) mean reductions in trough sitting diastolic and systolic BP were 15.0 +/- 7.1 mmHg (p < 0.01) and 20.8 +/- 16.7 mmHg (p < 0.01), respectively. There were no observed increases in drug-related adverse experiences in either study. Overall, the combination of losartan/hydrochlorothiazide was effective in lowering blood pressure and was well tolerated in patients with mild to moderate renal impairment.