Development of the isolated perfused porcine skin flap for in vitro studies of percutaneous absorption pharmacokinetics and cutaneous biotransformation
The isolated perfused porcine skin flap (IPPSF) has proven to be a valuable in vitro tool for studying the physiology and biochemistry of skin and for identifying biochemical and histological markers of direct cutaneous toxicity. The present experiments were undertaken for two purposes: (1) to develop a pharmacokinetic model, based on dermal penetration in the IPPSF, which is predictive of percutaneous absorption in vivo, and (2) to examine cutaneous biotransformation of the important agricultural poison parathion (P). Dosing solutions of {sup 14}C-radiolabelled compounds representing 3 chemical classes-organic acid/base (benzoic acid (B), caffeine (C)), organophosphate (OP) pesticides, and steroid hormones, were applied topically in ethanol at 40 {mu}m cm{sup {minus}2}, both in vivo and on the IPPSF. A 3-compartment pharmacokinetic model describing mass transfer from the surface (C{sub 1}), diffusion through epidermis and dermis (C{sub 2}), and transfer into the perfusate (C{sub 3}), was developed based on flux through the IPPSF from 0-8 hr. Model simulations were predictive of percutaneous absorption in vivo for the OP's and steroids. Modification of the basic 3-compartment model to account for fast and slow tissue-release processes (B) and for flux-dependent perfusage flow increases (C), provided excellent in vivo-in vitro correlation over all 7 compounds.
- Research Organization:
- North Carolina State Univ., Raleigh, NC (USA)
- OSTI ID:
- 5546792
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ABSORPTION
ANALEPTICS
ANIMALS
AROMATICS
AZAARENES
BENZOIC ACID
BIOCHEMISTRY
BIOLOGICAL MODELS
BODY
CAFFEINE
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM AGENTS
CHEMISTRY
DOMESTIC ANIMALS
DRUGS
ESTERS
HETEROCYCLIC COMPOUNDS
INSECTICIDES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MASS TRANSFER
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PARATHION
PESTICIDES
PHYSIOLOGY
PURINES
SKIN
SKIN ABSORPTION
STEROIDS
SWINE
THIOPHOSPHORIC ACID ESTERS
TRACER TECHNIQUES
UPTAKE
VERTEBRATES
XANTHINES