Abstract
Using excised human skin and tissue grafted to athymic mice, the in vitro and in vivo delivery and metabolism of a salicylate diester were compared. Concentration profiles of this drug and its metabolites were obtained for the outer several hundred microns of the skin. These results show significant differences in the extent of enzymatic cleavage and distribution of metabolites between in vitro and in vivo studies. Furthermore, these data suggest that in vitro results may overestimate metabolism because of increased enzymatic activity and/or decreased capillary removal.
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REFERENCES
D. R. Bickers. In V. A. Drill and P. Lazar (eds.), Current Concepts in Cutaneous Toxicology, Academic Press, New York, 1980, pp. 95–126.
D. A. W. Bucks. Pharm. Res. 1:148–153 (1984).
J. Hadgraft. In H. Bundgaard (ed.), Design of Prodrugs, Elsevier, Amsterdam, 1985, pp. 271–289.
J. Kao, J. Hall, and J. M. Holland. Toxicol. Appl. Pharmacol. 68:206–217 (1983).
J. M. Holland, J. Y. Kao, and M. J. Whitaker. Toxicol. Appl. Pharmacol. 72:272–280 (1984).
J. Kao, F. K. Patterson, and J. K. Hall. Toxicol. Appl. Pharmacol. 81:502–516 (1985).
J. Kao and J. Hall. J. Pharm. Exp. Ther. 241:482–487 (1987).
H. Mukhtar and D. R. Bickers. Drug Metab. Dispos. 11:562–567 (1983).
W. A. Khan, M. Das, S. Stick, S. Javed, D. R. Bickers, and H. Mukhtar. Biochem. Biophys. Res. Comm. 146:123–126 (1987).
Y. Ozawa, I. Koyama, S. Murayama, and T. Nadai. Chem. Pharm. Bull. 33:5113–5118 (1985).
W. Wiegrebe, A. Retzow, E. Plumier, N. Ersoy, A. Garbe, H.-P. Faro, and R. Kunert. Arzneim.-Forsch. 34:48–51 (1984).
G. G. Krueger, Z. J. Wojciechowski, S. A. Burton, A. Gilhan, S. E. Huether, L. G. Leonard, U. D. Rohr, T. J. Petelenz, W. I. Higuchi, and L. K. Pershing. Fund. Appl. Toxicol. 5:s112–s121 (1985).
M. Loden. J. Invest, Dermatol. 85:335–339 (1985).
K. H. Valia, T. Kakuji, and Y. W. Chien. Drug Dev. Ind. Pharm. 11:1133–1173 (1985).
K. Tojo, K. H. Valia, G. Chotani, and Y. W. Chien. Drug Dev. Ind. Pharm. 11:1175–1193 (1985).
J. L. Fox, C.-D. Yu, W. I. Higuchi, and N. F. H. Ho. Int. J. Pharm. 2:41–57 (1979).
R. H. Guy and J. Hadgraft. Int. J. Pharm. 11:187–197 (1982).
R. H. Guy and J. Hadgraft. In H. I. Maibach and N. Lowe (eds.), Models in Dermatology, Vol. 2, Karger, Basel, 1985, pp. 170–177.
J. Hadgraft. Int. J. Pharm. 4:229–239 (1980).
A. Zesch and H. Schaefer. Arch. Derm. Forsch. 246:335–354 (1973).
A. Zesch and H. Schaefer. Arch. Derm. Forsch. 252:245–256 (1975).
H. Schaefer, A. Zesch, and G. Stuttgen. Skin Permeability, Springer-Verlag, Berlin, 1982.
G. G. Krueger and R. A. Briggaman. In J. Fogh and B. P. Giovanella (eds.), The Nude Mouse in Experimental and Clinical Research, Vol. 2., Academic Press, New York, 1982, pp. 301–322.
A. Hoelgaard, B. Mollgaard, J. M. Anderson, and S. W. Kim (eds.). In Advances in Drug Delivery Systems, Elsevier, Amsterdam, 1986, pp. 111–120.
W. Smith. Ph.D. thesis, University of Michigan, Ann Arbor 1982.
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Guzek, D.B., Kennedy, A.H., McNeill, S.C. et al. Transdermal Drug Transport and Metabolism. I. Comparison of In Vitro and In Vivo Results. Pharm Res 6, 33–39 (1989). https://doi.org/10.1023/A:1015891400924
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DOI: https://doi.org/10.1023/A:1015891400924