Άκης
Administrator
Relationship between contact time of applied dose and percutaneous absorption of
minoxidil from a topical solution.
1: J Pharm Sci. 1990 Jun;79(6):483-6.
• Ferry JJ,• Shepard JH,• Szpunar GJ.
Clinical Pharmacokinetics Unit, Upjohn Company, Kalamazoo, MI 49001.
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 and minoxidil 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.
minoxidil from a topical solution.
1: J Pharm Sci. 1990 Jun;79(6):483-6.
• Ferry JJ,• Shepard JH,• Szpunar GJ.
Clinical Pharmacokinetics Unit, Upjohn Company, Kalamazoo, MI 49001.
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 and minoxidil 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.