20 LIJ LIJ lO o o lO 2o 3o 4o PC Figure 7. Effect of changes in partition coefficient on skin and blood values. Other parameters are same as in Figure 5. [], amount in skin at 12 hours /•, blood concentration at 12 hours. LIJ O ß I 0.00 0.01 0.02 K (1/min) Figure 8. Effect of changes in intercompartmental transfer coefficient on skin and blood values. Other parameters are same as in Figure 5. [], amount in skin at 12 hours &, blood concentration at 12 hours.

46 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Recently Rougier and co-workers described studies they conducted on short-term ap- plication of drug solutions to human volunteers and animals (6). The amount of radi- olabeled drug excreted over a four-day period after a 30-minute application was pro- portional to the amount obtained in skin strips following the same application time. This relationship held for several drugs at different applied concentrations, regardless of vehicle (6). Therefore, skin stripping experiments can be predictive of the total amount of a substance that will eventually be absorbed into the body. We were interested in exploring the effect of several parameters on excretion and blood values, using the simulation model to mimic conditions used by Rougier and co- workers. Figure 9 shows the relation between excretion and amount in the stratum corneum under conditions such that the only variable was the SC/vehicle partition coefficient. This corresponds to the use of different drugs or possibly the same drug in several vehicles with the varying solubility. As was shown by Rougier et al. (6), the amount excreted after four days is proportional to the amount in the stratum corneum. Furthermore, so are the peak blood concentrations (Figure 10). Figure 11 shows how differences in transport coefficient (K) affect 96-hour excretion values and p•ak blood levels. This amounts to comparing permeants that have different diffusion coefficients but the same partitioning behavior. The amount found in the stratum corneum was essentially the same in every case. Blood concentrations were O.OLO o.oo8 z I- o.oo6 x LLI 0.004 0.002 0.000 0.000 0.002 0.004 0.006 0.008 0.010 SC AMOUNT Figure 9. Amount excreted in urine at 96 hours versus amount in the stratum corneum at 30 minutes, both following 30-minute application, for various values of PC. (K = 0.02 min-• donor concentration = 10 mg/ml donor volume = 5 •1 elimination rate constant = 0.0016 min-• volume of distribution = 5000 ml).