Drug and vehicle deposition from topical applications: localization of minoxidil within skin strata of the hairless mouse.
The cutaneous bioavailability of topical 2% minoxidil solution was verified in live hairless mice. Minoxidil and propylene glycol deposition on the skin surface, epidermis and dermis from the single-dose in vivo study were compared with the results from previous in vitro studies. A distinct difference is apparent in the epidermis where the in vitro values are 11-22 times higher than the in vivo values for minoxidil and 8-16 times higher for propylene glycol. The differences were not as great in the dermis. Percutaneous absorption of the drug appeared to be a very small fraction of the applied dose. Similarly shaped stratum corneum and plasma concentration profiles and the relatively constant dermal profiles of minoxidil and propylene glycol open the possibility of transappendageal routes being involved in percutaneous absorption. The greater amount of drug and vehicle found in the dermis from in vitro studies can be explained by the absence of dermal clearance. The overestimation in the amount of drug found in the epidermis in vitro may also be attributable to poor dermal clearance. On the whole, the study raises questions about the use of in vitro tissue dispositions for bioavailability assessment and bioequivalence demonstration.
Tsai
J C
JC
College of Pharmacy, University of Michigan, Ann Arbor 48109.
Weiner
N
N
Flynn
G L
GL
Ferry
J J
JJ
D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D004817:Epidermis / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008914:Minoxidil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000493:pharmacokinetics; D019946:Propylene Glycol; D011409:Propylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012869:Skin Absorption
D014677:Pharmaceutical Vehicles; D011409:Propylene Glycols; D008914:Minoxidil; D019946:Propylene Glycol