Evaluation of in-vitro percutaneous absorption across human skin and in animal models.
The in-vitro permeability characteristics of human skin have been examined and compared with results in laboratory animals using various types of penetration enhancers. The study was focused on evaluation of predictable validity of the data obtained in animals mostly used in permeation studies. The results in man using the same penetration enhancers were about 30% of the value in the rat. The least potent enhancer was dimethylsulphoxide and the maximum efficacy was observed with sodium laurylsulphate in the rat experiments while in man the results were approximately equal when using any of the studied enhancers. Comparison of the results of experiments performed with N-methyl-2-pyrrolidone in several laboratory animals and man showed that the skin permeability in man is approximately 4 times lower than with the rat. Man and guinea-pig were not significantly different in these experiments. There were no significant differences in laurocapram penetration enhancing effect in the concentration range 0.1 to 0.5%, but there was an optimum concentration of laurocapram of 1%. The results showed quantitative differences in percutaneous absorption in various animal species in comparison with man. These differences should be considered in selecting a suitable model for preclinical drug evaluation. The guinea-pig skin penetration seems to be most similar to that in man.
Príborský
J
J
Institute of Pharmacology, Medical Faculty of Hygiene, Charles University, Prague, Czechoslovakia.
Mühlbachová
E
E
D000328:Adult; D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005069:Evaluation Studies as Topic; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008875:Middle Aged; D011760:Pyrrolidinones / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption / Q000187:drug effects*; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013045:Species Specificity; D013552:Swine; D013997:Time Factors
D011760:Pyrrolidinones; D012967:Sodium Dodecyl Sulfate; C038678:N-methylpyrrolidone; D004121:Dimethyl Sulfoxide