The Pharmacokinetics of 2.5‐ to 10‐mg Oral Doses of Minoxidil in Healthy Volunteers

The dose proportionality of minoxidil was investigated by studying its pharmacokinetics after administration of single, oral doses of 2.5, 5.0, and 10.0 mg. The study, which was a Latin square cross‐over design, was performed in 30 young, nonobese, normal subjects. Treatments were separated by a 4‐day washout period. Serum and urine levels of minoxidil were determined by high‐performance liquid chromatography (HPLC) and radioimmunoassay (RIA). Supine blood pressure and pulse were monitored during each study phase. Minoxidil concentrations determined by RIA were highly correlated with concentrations determined by HPLC; only the HPLC data was used in the pharmacokinetic analyses. No significant effects were observed for dose normalized C max , t max , volume of distribution, minoxidil renal clearance, or the percentage of the dose excreted as either minoxidil or minoxidil glucuronide. Significant differences in apparent oral clearance, dose normalized AUC, and terminal elimination rate constant (β) were observed between the 2.5‐mg dose and the higher doses, but no differences in these parameters between the 5.0‐ and 10.0‐mg doses were apparent. Thus, the available data support dose‐independent pharmacokinetics for minoxidil over this range of doses. Repeated measures analysis of variance detected significant time and treatment effects on supine blood pressure and pulse rate, but the effects were generally small and of little clinical significance. The results support the hypothesis that minoxidil has little effect on blood pressure in normotensive subjects.