Pharmacokinetic studies of minoxidil

The disposition of minoxidil, a new direct arterial vasodilator and potent antihypertensive, was studied in 7 hypertensive patients. Following oral administration of 14 C‐labeled minoxidil, there was a rapid removal of the drug with a plasma half‐life of 4.2 hours. The radioactive label was recovered quantitatively in the urine, predominantly in the form of 3 metabolites. The major metabolite in the first 12 hours after giving the drug was a glucuronide conjugate. The other 2 metabolites have not been identified but appeared to be excreted predominantly after the first 12 hours, when minoxidil had been essentially cleared from the circulating blood. These observations suggest a dissociation between the drug in circulating blood and its pharmacologic activity. Since the prolonged hypotensive response to minoxidil cannot be attributed to slow removal, we suggest that it may be exerting a persistent effect on receptor sites.