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j. $oc. Cosmet. Chem., 30, 297-307 (September/October 1979) Recent advances in percutaneous absorption using the rhesus monkey model RONALD C. WESTER and PATRICK K. NOONAN Department of Drug Metabolism, G. D. Searle and Company, Skokie, IL 60077, and HOWARD I. MAIBACH Department of Dermatology, University of California School of Medicine, San Francisco, CA 94143. Received April 10, •979. Presented at Annual Scientific Seminar, Society of Cosmetic Chemists, May 1979, Dallas, Texas. Synopsis PERCUTANEOUS ABSORPTION in non-primate laboratory animals has been shown to be different from man. This report REVIEWS STUDIES in which skin absorption in the RHESUS MONKEY was shown to be similar to man. This animal MODEL was then used in a series of studies on factors affecting skin absorption. The amount of compound absorbed through the skin was shown to be dependent on the topical concentration applied to the skin. Also, the frequency of daily application affected absorption a single large dose had greater absorption than equivalent divided doses applied at more frequent intervals. Additionally, acute versus chronic topical dosing was compared. Penetration is routinely measured by acute administration. However, the absorption of hydrocortisone significantly increased during chronic administration. This suggests that chronic application of hydrocortisone alters the penetration barrier resulting in enhanced absorption. Salicylic acid was thought to enhance the penetration of other compounds through its keratolytic action. However, in a single dose application study, the addition of salicylic acid, at equal to or ten times the concentration of hydrocortisone, did not enhance the absorption of hydrocortisone. Toxicity from topical compounds is critical in the newborn. The same high percentage of asteroid that can be absorbed through the skin of an adult can be absorbed in a newborn. This could become critical in a newborn because the ratio of surface to body weight is three times that of the adult. The therapeutic ratio probably is lower in the newborn than in the adult when the compound is applied topically. INTRODUCTION This paper discusses some recent work using the rhesus monkey as an animal model for percutaneous absorption. First we compare percutaneous absorption in the rhesus monkey and other animal models to that in man. We then review recent studies performed with the rhesus in which the experimental design was changed from the usual procedure of applying a single topical dose, to designs which may be more 297