Pinacidil with and without hydrochlorothiazide. Dose-response relationships from results of a 4 x 3 factorial design study

Abstract

Utilising a modified fixed-dose, 4 x 3 factorial design, the antihypertensive effects of all combinations of 4 doses of pinacidil (0, 12.5, 25 and 37.5 mg bid) with 3 doses of hydrochlorothiazide (0, 12.5 and 25 mg bid) were studied in patients with supine diastolic blood pressure of 95 to 110mm Hg. The decreases in supine diastolic blood pressure from baseline were dose-related for both drugs. The response to the highest monotherapy dose of pinacidil was less in patients with oedema. When given in combination, hydrochlorothiazide blunted the differences among pinacidil doses so that 12.5 mg pinacidil with 12.5mg hydrochlorothiazide administered twice daily produced nearly maximal antihypertensive efficacy. For pinacidil monotherapy, the incidence of oedema was 3%, 26% and 47% at dosages of 12.5, 25, and 37.5mg bid, respectively, with significant attenuation of these effects at both hydrochlorothiazide dosage levels. Based upon these data, low (12.5-25mg bid) doses of pinacidil are effective and safe as monotherapy for hypertension. The optimal combination of pinacidil with hydrochlorothiazide given twice daily for hypertension contains 12.5mg of each drug.