Percutaneous absorption kinetics of topical metronidazole formulations in vitro in the human cadaver skin model.
Topical formulations containing identical active agents are available in various vehicles and concentrations, which may affect percutaneous absorption. This study was undertaken to evaluate the in vitro percutaneous absorption pharmacokinetics of metronidazole in different vehicles and concentrations as the active agent in 6 topical formulations. Formulations were applied to sections from 3 cadaver skin donors, and percutaneous absorption of metronidazole was measured over a 48-h test period through the finite dose technique and the use of Franz diffusion cells. Metronidazole penetrates into and through human cadaver skin. Data show the general ranking of delivery of similar concentrations of metronidazole according to vehicle as cream > lotion > gel. The 48-h penetration of metronidazole in the human cadaver skin model was greatest with cream formulations and lowest with gel formulations. These results reveal the importance of the vehicle selected for penetration of metronidazole into the skin. The relevant target zone in rosacea is the dermis because this is the area where inflammation takes place. Additional studies are warranted to examine absorption of metronidazole into the relevant target zone and the correlation of absorption with efficacy.
Elewski
Boni E
BE
Department of Dermatology, University of Alabama School of Medicine, Birmingham, AL 35294-0009, USA. beelewski@aol.com
D000328:Adult; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D002102:Cadaver; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D004305:Dose-Response Relationship, Drug; D005260:Female; D005782:Gels; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008795:Metronidazole / Q000493:pharmacokinetics*; D008875:Middle Aged; D014677:Pharmaceutical Vehicles; D012869:Skin Absorption / Q000187:drug effects*
D000890:Anti-Infective Agents; D004304:Dosage Forms; D005782:Gels; D014677:Pharmaceutical Vehicles; D008795:Metronidazole