PERCUTANEOUS ABSORPTION OF DRUGS 377 These equations clearly indicate that the extent of absorption of the acids into human skin is primarily determined by their lipophilic character as meas- ured by log P in octanol/water or benzene/water systems. More than 80% of the variance in the data (r 2 0.80) can be accounted for by these equa- tions. The (log P)2 term in eq 2 is not statistically significant nevertheless, the optimum lipophilic character [log Po, obtained by setting d (log C)/ d(log P) = 0] for maximum absorption is around 2.67, very close to the pene- tration of the brain by the same series of compounds (log Po = 2.3), and the maximum hypnotic effect of barbiturates (log Po = 2.4) (9). Addition of the HammeWs cr constant to eq i does not result in a significant improvement in correlation. If one considers that both the neuroglia (blood-brain barrier) and the skin are evolved from the same embroyonic origin, namely, the ectoder- mal layer, these findings may have some biological implications. A better selection of compounds with wider log P values to establish the 95% confi- dence interval of the log Po value should verify the true log Po value for maxi- mum percutaneous absorption. Equations 4-9 are derived from the permeability of rabbit whole skin to nonelectrolytes like alcohol, urea, and glucose, while eqs 10-12 are from the permeability through rabbit dermis: log Kv(cm/hr) = -1.006 log MW - 1.371 (4) (n = 7, r = 0.349, s = 0.803) log K v(cm/hr) = -1.836 log MRa - 0.982 (5) (n = 7, r = 0.509, s = 0.787) log Kv (cm/hr) = 0.392 log r - 2.761 (6) (n = 7, r = 0.928, s = 0.318) log K v(cm/hr) - -0.060 (log p)2 + 0.309 (log P) - 2.591 (7) (n = 7, r = 0.957, s = 0.278, log Po = 2.55 +- •) log K• (cm/hr) = 0.360 log P - 0.964 log MRa - 1.599 (8) (n = 7, r = 0.963, s = 0.257) log K v(cm/hr) = 0.385 log P - 0.856 log MW - 1.151 (9) (n = 7, r = 0.975, s = 0.214) log K v (cm/hr) -- 0.100 log P - 0.970 (10) (n = 6, r = 0.823, s = 0.097) log K.(cm/hr) = -0.622 log MRa - 0.395 (11) (n = 6, r = 0.931, s = 0.062) log K v (cm/hr) = -0.575 log MW - 0.098 (12) (n = 6, r = 0.982, s = 0.032)

378 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS