Serum concentration and antihypertensive effect of slow-release verapamil

Serum concentrations of verapamil and its main metabolite norverapamil as measured by high-pressure liquid chromatography were compared with blood pressure responses to long-term antihypertensive therapy with a slow-release formulation of verapamil (120-240 mg b.d.) in 14 patients with essential hypertension. Trough and peak verapamil concentrations varied widely, but in individual patients relatively stable drug levels were maintained up to 8 h after a morning dose. Even at 24 h verapamil concentrations greater than 50 ng/ml were present in 11 of 14 cases. Norverapamil concentrations were higher than those of the parent drug throughout the entire dosage interval. Blood pressure reduction less than or equal to 160/95 mm Hg was achieved in 13 patients by verapamil alone, but a direct relationship between drug levels and antihypertensive effects or the patient's age was not demonstrable. Despite a marked decrease of verapamil concentrations, blood pressure reduction persisted up to 24 h after the last dose. Thus, after repetitive dosing of slow-release verapamil, adequate blood pressure control is achieved by giving the drug twice (or perhaps once) daily.