The efficacy and safety of captopril were studied in 10 patients with secondary hypertension (renal parenchymal disease, four patients; renal artery stenosis, two; and renal transplant rejection, four). Captopril was administered according to a dose titration protocol that randomized the initial three doses (0.5, 1.0, and 2.0 mg/kg) of drug to one of six possible sequences. All patients received diuretics prior to and during captopril therapy. A significant reduction in mean blood pressure was observed in all 10 patients during the initial dose titration. No correlation was observed between captopril dose and magnitude of the blood pressure reduction. The onset of antihypertensive action began approximately 15 minutes after each orally administered dose and reached the nadir approximately 1 1/2 hours later. Blood pressure returned to predrug levels between 6 and 10 hours after the dose. A significant reduction in systolic and diastolic blood pressure was noted in all subjects after 1 week of captopril treatment and was maintained during the course of continuous therapy in nine of 10 patients. Captopril combined with hydrochlorothiazide produced a satisfactory therapeutic response in five patients; in four others, additional antihypertensive drugs were required. No significant adverse effects were observed. Plasma renin activity determined prior to initiation of captopril was not predictive of blood pressure response to the drug. The clearance of captopril from patients with kidney failure ranged from 14.1 to 18.8 ml/min/kg in five subjects with creatine clearance between 10 and 21 ml/min/1.73 m2.
Bibliographical noteFunding Information:
From the Division of Clinical Pharmacology, Departments of Pediatrics and Pharmacology, University of Minnesota. Dr. O'Dea supported by Research Career Development Award HL-00565 from the National Heart, Lung and Blood Institute, National Institutes of Health. Reprint requests: Alan R. Sinaiko, M.D., Division of Clinical Pharmacology, University of Minnesota Medical School, 3-260 Millard Hall, 435 Delaware St. S.E., Minneapolis, MN 55455.