THE RATE OF PERCUTANEOUS PERMEATION OF XYLENE, MEASURED USING THE PERFUSED PIG EAR MODEL, IS DEPENDENT ON THE EFFECTIVE PROTEIN-CONCENTRATION IN THE PERFUSING MEDIUM

In order to study the dermal permeation of compounds through the skin, an in vitro model was developed which utilized pig ears perfused with autologous pig blood (de Lange, J., van Eck, P., Elliott, G. R., de K ort, W. L. A. M., and Wolthuis, O. L. (1992). J. Pharmacol. Toxicol. M ethods 27, 71-77). In the present article we investigated to what exte nt the rate of permeation of xylene through pig ear skin is dependent on the perfusion medium used. Pig ears were exposed to xylene (10 cm(2 ) area) for a 4-hr period (30 degrees C, relative humidity of 40-60%) and the perfusate was analyzed for xylene using gas chromatography. Th e rates of permeation of xylene for whole blood, blood depleted of whi te blood cells, and a buffer containing 4.5% albumin were similar (+/- 300 ng/min/cm(2)). The rate of penetration was fivefold higher when pi g plasma was used and ninefold lower when albumin was excluded from th e buffer. Using the buffer, we found that the rate of permeation of xy lene was proportional to flow (constant protein concentration) and pro tein concentration (constant flow). Our data demonstrate that the meas ured permeation rate for xylene is, to a large degree, dependent on th e effective protein concentration (mg/min) passing through the ear. Di fferences in this parameter could explain the variations in rates of p ermeation found using the different perfusion media. To avoid problems associated with the choice of receptor fluid for permeation experimen ts, we suggest that full blood remains the vehicle of choice, although the practical perfusion period is limited to about 6 hr. If longer pe rfusion periods are required, then it should be possible to reproduce results obtained with whole blood by choosing an appropriate buffer. ( C) 1994 Academic Press, Inc.