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Relationship between contact time of applied dose and percutaneous absorption of minoxidil from a topical solution


Twenty-two healthy male volunteers completed a four-way, multiple-dose, randomized crossover study to determine the relationship between contact time of applied drug on the scalp andminoxidil absorption from a 2% topical solution. One milliliter of solution was applied twice daily over 150 cm2 of bald scalp to each subject for 6 days. Unabsorbed drug was washed off the scalp after 1, 2, 4, and 11.5 h of contact time in each of four treatments. Cumulative urinary excretion profiles within steady-state, 12-h dosing intervals were well described by straight lines for all treatments, indicating that systemic minoxidil elimination was rate controlled by constant, zero-order percutaneous drug absorption. The extent of minoxidil absorption, expressed as steady-state urinary excretion of unchanged minoxidil, minoxidil glucuronide, or the sum of these, increased in a disproportionate manner with increase in contact time of drug on the scalp. Relative to the amount absorbed after a contact time of 11.5 h, absorption was approximately 50% complete by 1 h and greater than 75% complete by 4 h. This suggests that minoxidil absorption from the vehicle into skin occurs rapidly relative to diffusion through skin. The rate of minoxidil absorption from vehicle into skin was characterized as nonlinear, whereas minoxidil excretion into urine was rate controlled by diffusion from one or more components of the skin which apparently serve as a reservoir, or depot, for minoxidil.



Ferry JJ; Shepard JH; Szpunar GJ;



J Pharm Sci, 79(6):483-6 1990 Jun



Clinical Pharmacokinetics Unit, Upjohn Company, Kalamazoo, MI 49001.





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