Estimation of the plasma concentration and course of action of phentolamine based on its inhibitory effect on adrenaline-induced platelet aggregation.

Orally administered phentolamine retards the first phase of adrenaline-induced platelet aggregation. The extent to which aggregation was inhibited was compared in blood samples from six healthy volunteers treated with phentolamine and samples to which various concentrations of the drug were added These experiments permitted conclusions to be drawn concerning the magnitude and time-course of the plasma concentrations reached after the administration of phentolamine. A dose of 40 mg of the standard formulation (SF) produced a maximum effect after 30 min corresponding to that of a phentolamine concentration of approximately 12 × 10 M (≈34 ng/ml). After 3 h about one-third of the maximum effect persisted, and after 6 h only a slight degree of activity was still detectable. The slow-release formulation (SR) (100 and 200 mg) had a rapid onset of action (1 h); the maximum effect was observed after 4 h, corresponding to an estimated plasma concentration of phentolamine of 11 and 42 ng/ml respectively, and the duration of action was well in excess of 12 h. The time-course of the increase in heart rate and the increase in myocardial contractility (as determined from the pre-ejection period) was largely consistent with the calculated time-course of the plasma concentrations: A dose of 40 mg SF produced its maximum effect after 30-60 min and had a duration of action of 3 h. The maximum effect of the SR formulation was reached after 4 h, and the duration of action was more than 10 h.