Chemical structure - transport rate relationships for model skin lipid membranes.
Houk-J; Hansch-C; Hall-LL; Guy-RH
Altern Methods Toxicol 1987 Jan; 5:341-352
Model lipid membrane systems were studied in relation to chemical structure transport rate relationships applicable to the prediction of drug absorption through human skin. The model skin lipid transport system incorporated a rotating diffusion cell comprised of a donor compartment containing a solution of penetrant in water or aqueous buffer, a receptor compartment containing the same solution without penetrant, and a lipid membrane between the compartments made up of an organic liquid supported within a cellulose-ester filter with a pore size of 0.22 micrometers. The organic liquid membranes used were isopropyl-myristate (IPM) and tetradecane, and the penetrants tested included various esters of nicotinic-acid and phenol derivatives. A nonlinear quadratic relationship was determined for the logarithm of the experimental transport resistances and the logarithm of the octanol/water partition coefficients. The results were comparable to data obtained from the in-vitro transport of phenols through excised human cadaver skin. The authors conclude that the model skin lipid membranes mimic the in-vitro resistance of human skin and do not limit transport solely through simple diffusional resistance.
NIOSH-Grant; Dermatitis; Skin-absorption; Simulation-methods; Analytical-models; Drug-therapy; Therapeutic-agents; Pharmacodynamics; Biokinetics
Pharmacy University of California 926 Medical Sciences Building San Francisco, Calif 94143
Alternative Methods in Toxicology, Vol. 5, In Vitro Toxicology - Approaches to Validation
University of California San Francisco, San Francisco, California