Seventeen patients with mild to moderate
hypertension, as indicated by a diastolic blood pressure (DPB) of 95-115 mmHg (WHO I), were treated in a randomized, double-blind, parallel study, with either 5 mg of
fosinopril, a new
phosphinic acid-containing
angiotensin converting enzyme (
ACE) inhibitor, or 25 mg of
hydrochlorothiazide administered orally once daily for 4 weeks after a 4- to 6-week run-in period of placebo. The doses were increased to 10 mg of
fosinopril or 50 mg of
hydrochlorothiazide if DBP remained above 95 mmHg. The blood pressure (BP) fell from 157 +/- 12/104 +/- 7 mmHg (mean value +/- SD) at the start of the study to 146 +/- 21/97 +/- 8 mmHg (P less than 0.02) after 4 weeks, and to 149 +/- 19/97 +/- 7 mmHg (P less than 0.02) after 8 weeks of
fosinopril treatment (n = 8). In the
hydrochlorothiazide-treated patients (n = 9), BP fell from 153 +/- 9/105 +/- 5 mmHg at the start of the study to 140 +/- 11/97 +/- 7 mmHg (P less than 0.01) after 4 weeks, and to 131 +/- 11/94 +/- 7 mmHg (P less than 0.01) after 8 weeks. After the first dose, DBP fell from 102 to 99 mmHg (NS) in
fosinopril-treated patients, and from 105 to 96 mmHg (P less than 0.02) in
hydrochlorothiazide-treated subjects. Serum active fosinoprilate concentration increased to 5.6 ng ml-1, 25.9 ng ml-1, and 43.8 ng ml-1 after 30, 60 and 120 min, respectively, and remained at a level of 6.6-7.7 ng ml-1 after 4 and 8 weeks, respectively. Serum ACE activity decreased from 21.6 +/- 11.0 mumol min-1 l-1 at the start to 9.3 +/- 13.7, 4.4 +/- 4.6, and 2.9 +/- 2.8 mumol min-1 l-1 after 30, 60 and 120 min, respectively. No side-effects and no changes in blood counts,
electrolytes or kidney function were attributed to
fosinopril during the study.
Fosinopril is a safe, long-acting
antihypertensive drug with a smooth onset of action.
Hydrochlorothiazide treatment caused
potassium loss and an increase in the levels of
uric acid and
triglycerides. Diastolic blood pressure decreased to the same extent as a result of treatment with either drug, while systolic blood pressure was better controlled by
hydrochlorothiazide.