Pharmacodynamics of minoxidil as a guide for individualizing dosage regimens in hypertension

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Abstract
The antihypertensive effect of minoxidil was studied in 6 patients with varying degrees of hypertension. Their baseline mean arterial pressure (MAPbl) ranged from 122 to 197 mm Hg. Single oral doses between 2.5 and 25 mg were administered in sequence and the time‐course of hypotensive action was followed. We have reported previously that when the peak lowering of MAP is linearly regressed against log dose, both the dose‐response slope (M) and threshold dose (Dt) are positively correlated with the MAPbl of individual patients. This investigation focuses on the temporal pattern of effect. It was found that the hypotensive effect of minoxidil declined linearly with time at a rate consistent with an average effective biologic half‐life of about one day. The rate of decline of effect was apparently independent of dose but was dependent on MAPbl. Since both response to and duration of effect of minoxidil are functions of MAPbl, there is an obvious need to individualize dosage regimens based on the severity of disease. Using pharmacodynamic parameters, guidelines for loading dose, maintenance dose, and dosing frequency as a function of the degree of hypertension are suggested. Loading dose requirements were found to increase with MAPbl while maintenance doses were largely independent of the severity of the disease. Frequency of dosing was found to range from 3 times a day in very severe hypertension to once a day in moderate hypertension.

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