SYNERGY OF PRESERVATIVES 365 (35) R. Y. Lochhead, W. J. Hemker, and J. Y. Castafieda, Hydrophobically modified "carbopol" resins, Soap/Cosmet./Chem. Special., 63(5), 28, 29, 32, 33, 84, 85 (1987). (36) F. W. Adair, S. G. Geftic, and H. Heymann, Lytic effect of di- or tricarboxylic acids plus sodium dodecyl sulfate against Pseudomonas aeruginosa, Antimicrobial Agents Chemother., 16, 417-420 (1979). (37) R. M. E. Richards and M.P. Hardie, Effect ofpolysorbate 80 and phenylethanol on the antibacterial activity of fentichlor, J. Pharm. Pharmac., 24 (Suppl.), 90P-93P (1972). (38) M. J. Akers, A. V. Boand, and D. A. Binkley, Preformulation method for parenteral preservative efficacy evaluation, J. Pharm. Sci., 73, 903-905 (1984). (39) W. B. Hugo and A.D. Russell, "Evaluation of Non-Antibiotic Antimicrobial Agents," in Pharma- ceutical Microbiology, 4th ed., W. B. Hugo and A. D. Russell, Eds. (Blackwell Scientific Publica- tions, Oxford, England, 1988), pp. 253-280.

J. Soc. Cosmet. Chem., 40, 367-373 (November/December 1989) Skin stripping as a potential method to determine in vivo cutaneous metabolism of topically applied drugs JOHANN W. WIECHERS, RENELLA E. HERDER, BEN F. H. DRENTH, and ROKUS A. de ZEEUW, Groningen Centre for Drug Research, Bioanalysis and Toxicology Group, University of Groningen, A. Deusinglaan 2, 9713 A W Groningen, The Netherlands. Received August 25, 1989. Synopsis By chromatographing an extract of the tapes obtained in a skin stripping procedure, cutaneous metabolism of compounds after topical administration may be observable, provided that outward transdermal migration occurs. This method may be helpful, especially in situations where no differentiation between cutaneous and systemic metabolism can be made due to the experimental design or the very low systemic concentra- tions. Through use of this methodology, it can be assessed that the penetration enhancer for percutaneous absorption, Azone ©, is only present as the parent compound in the stratum corneum, whereas the anti-acne agent Cyoctol undergoes cutaneous biotransformation during skin passage. INTRODUCTION In recent years there has been a renewed and growing interest in dermal and trans- dermal drug delivery. This route opens new possibilities for systemic therapy, especially for drugs with short biological half-lives due to extensive first-pass metabolism in the liver. Compounds, however, may also be metabolized in the skin before reaching the systemic circulation (1,2), thereby reducing their bioavailability. For this reason, the cutaneous metabolism of these compounds should be studied and compared to already available systemic biotransformation data. If cutaneous metabolism occurs, additional investigations may be required to determine the pharmacological profile of the dermally formed metabolites. A simple method to establish in vivo cutaneous metabolism of topically applied agents was developed and will be discussed on the basis of two compounds currently under investigation in our laboratories, Azone © and Cyoctol. Both compounds are to exert their action in human skin, Azone as a penetration enhancer for percutaneous absorp- Johann W. Wiechers' present address is Unilever Research, Colworth Laboratory, Sharnbrook, Bedford MK44 1LQ, United Kingdom. 367