Diffusion of (2-/sup 14/C)diazepam across hairless mouse skin and human skin

Journal Article · Fri May 01 04:00:00 EDT 1987 · J. Invest. Dermatol.; (United States)

DOI:https://doi.org/10.1111/1523-1747.ep12470195· OSTI ID:6501056

Koch, R L; Palicharla, P; Groves, M J

The objectives of this study were to investigate the absorption of diazepam applied topically to the hairless mouse in vivo and to determine the diffusion of diazepam across isolated hairless mouse skin and human skin. (/sup 14/C)Diazepam was readily absorbed after topical administration to the intact hairless mouse, a total of 75.8% of the /sup 14/C-label applied being recovered in urine and feces. Diazepam was found to diffuse across human and hairless mouse skin unchanged in experiments with twin-chambered diffusion cells. The variation in diffusion rate or the flux for both human and mouse tissues was greater among specimens than between duplicate or triplicate trials for a single specimen. Fluxes for mouse skin (stratum corneum, epidermis, and dermis) were greater than for human skin (stratum corneum and epidermis): 0.35-0.61 microgram/cm2/h for mouse skin vs 0.24-0.42 microgram/cm2/h for human skin. The permeability coefficients for mouse skin ranged from 1.4-2.4 X 10(-2)cm/h compared with 0.8-1.4 X 10(-2)cm/h for human skin. Although human stratum corneum is almost twice the thickness of that of the hairless mouse, the diffusion coefficients for human skin were 3-12 times greater (0.76-3.31 X 10(-6) cm2/h for human skin vs 0.12-0.27 X 10(-6) cm2/h for hairless mouse) because of a shorter lag time for diffusion across human skin. These differences between the diffusion coefficients and diffusion rates (or permeability coefficients) suggest that the presence of the dermis may present some barrier properties. In vitro the dermis may require complete saturation before the diazepam can be detected in the receiving chamber.

• Research Organization: Univ. of Illinois, Chicago
• OSTI ID: 6501056
• Journal Information: J. Invest. Dermatol.; (United States), Journal Name: J. Invest. Dermatol.; (United States) Vol. 5; ISSN JIDEA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ABSORPTION
ANIMALS
BODY
CARBON 14 COMPOUNDS
CENTRAL NERVOUS SYSTEM AGENTS
DIFFUSION
DRUGS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MAN
METABOLISM
MICE
ORGANS
PERMEABILITY
PRIMATES
PSYCHOTROPIC DRUGS
RODENTS
SKIN
SKIN ABSORPTION
TRACER TECHNIQUES
TRANQUILIZERS
UPTAKE
VERTEBRATES