In vitro percutaneous penetration: evaluation of the utility of hairless mouse skin.
The permeability barrier of hairless mouse skin has been determined in vitro after exposure of the epidermal surface to volumes of acetone typically used in human in vivo skin penetration studies. It has been shown that the transport of tritiated water (when applied for limited 5-h periods) across hairless mouse skin is not affected by acetone treatments of approximately 15 microliters/cm2. Submersion of the membranes between aqueous donor and receptor phases for periods greater than 24 h, however, leads to significant and catastrophic barrier impairment. The acetone dose in the experiments reported is greater than that employed in vivo when the solvent is used to deposit a penetrant on human skin. We suggest, therefore, that acetone-mediated facilitation of percutaneous absorption in humans is unlikely. A further conclusion of this work is that in vitro solvent-deposition penetration experiments using hairless mouse skin should provide reliable transport information for at least 48 h postadministration. Although hairless mouse skin is more permeable than its human counterpart, in vitro measurements using the murine barrier should, therefore, provide useful and relevant guidelines for risk assessment calculations and bioavailability determinations.
Hinz
R S
RS
Department of Pharmacy, University of California, San Francisco 94143-0446.
Hodson
C D
CD
Lorence
C R
CR
Guy
R H
RH
D000042:Absorption; D000096:Acetone / Q000494:pharmacology; D000818:Animals; D001834:Body Water / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008812:Mice, Hairless / Q000378:metabolism*; D010539:Permeability; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D014867:Water / Q000494:pharmacology
D014867:Water; D000096:Acetone