title: The effects of equine skin preparation on transdermal drug penetration in vitro.
abstract: An increasing number of formulations are applied to equine skin, yet variable penetration can affect efficacy, or the incidence of adverse effects, or both. To investigate the effects of common methods of skin preparation on transdermal drug penetration in vitro, we clipped, harvested, and froze skin samples from 5 Thoroughbred geldings. Thawed samples were prepared as follows: control (no preparation); cleaned with aqueous chlorhexidine (Aq-C, 0.1% w/v); cleaned with alcoholic chlorhexidine (Al-C, 0.5% w/v); shaved (Sh); or tape-stripped (Ta) with the use of adhesive tape. The samples were then placed in diffusion cells, and 2 g of methylsalicylate (MeSa) gel (Dencorub) was applied to the stratum corneum side. The penetration of MeSa and its analyte, salicylate (Sa), through the skin samples was measured over 10 h. Compared with control skin, significantly more MeSa penetrated through skin prepared with Al-C or Sh (P < 0.01) or with Aq-C or Ta (P < 0.05), and significantly more Sa was recovered in the receptor phase from skin prepared with Aq-C, Al-C, or Sh (P < 0.05) or with Ta (P < 0.01). A significantly higher rate of penetration and shorter lag time were also noted for MeSa with all the prepared skin samples, compared with the control samples. The results show that clinical techniques routinely used to clean or prepare skin can significantly affect the rate and extent of penetration of a topically applied drug. This may result in greater systemic availability of active drug, which could lead to enhanced efficacy and, possibly, a higher incidence of adverse effects.
authors.affiliation: School of Veterinary Science, University of Queensland, Brisbane, Queensland 4072, Australia. p.mills@uq.edu.au
authors.forename: Paul C
authors.initials: PC
authors.lastname: Mills
authors.forename: Sheree E
authors.initials: SE
authors.lastname: Cross
mesh_terms: D000279:Administration, Cutaneous; D000287:Administration, Topical; D000818:Animals; D019540:Area Under Curve; D002710:Chlorhexidine / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D006197:Hair / Q000502:physiology; D006736:Horses; D066298:In Vitro Techniques; D008297:Male; D012459:Salicylates / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology*
chemical_list: D012459:Salicylates; D000431:Ethanol; C033069:methyl salicylate; D002710:Chlorhexidine