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j. Soc. Cosmet. Chem., 35, 103-113 (March/April 1984) Percutaneous absorption kinetics of topically applied agents liable to surface loss RICHARD H. GUY, Department of Pharmacy and Pharmaceutical Chemistry, School of Pharmacy, University of California at San Francisco, San Francisco, CA 94143, and JONATHAN HADGRAFT, Department of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom. Received April 21, 1983. Synopsis Simple, physicaliy based, models are given for evaluating the percutaneous absorption kinetics of topically applied agents liable to surface loss, e.g. insect repellants and sunscreen agents. Disappearance from the skin surface is simulated by either zero-order or first-order kinetics. Absorption of the topically applied agent into the body is treated as two consecutive first-order processes, one of which relates to transport across the stratum corneum, the other to movement from the horny layer to the blood. Solutions to the kinetic equations of the models are detailed which describe the relative surface and strattun corneum concentrations of the applied material. Using representative, published, values for the rate parameters of the simulation, surface and strattun corneum concentration-time profiles are calculated that cover a wide range of potential applications. Quantitative assessments of situations, for which surface loss kinetics may assume importance in terms of the applied agent's desired physiological or protective effects, are thus presented. INTRODUCTION Agents, which are topically applied to the skin of man, are administered with a variety of different objectives. Clinically, the goal of the physician is to promote partial or total percutaneous absorption so that either local or systemic chemotherapeutic effects may be elicited. The formulation of a sunscreen or insect repellent or fragrance, on the other hand, requires the active chemical to penetrate less efficiently and remain localized close to the skin surface for an extended period. However, for both of the examples quoted above, success of the various treatments may be compromised by the competitive surface loss of applied material. The mechanisms by which topically applied agents may be removed after administration are diverse. There exists, of course, the natural desquamation process of the stratum corneum by which, on average, one cell layer per day is shed (corresponding to a complete turnover of the horny layer approximately once every 2-3 weeks) (1,2). Equally, in acting as the body's interface with the environment, the skin surface is constantly under physi- 103