THE ISOLATED-PERFUSED BOVINE UDDER AS AN IN-VITRO MODEL OF PERCUTANEOUS DRUG ABSORPTION SKIN VIABILITY AND PERCUTANEOUS-ABSORPTION OF DEXAMETHASONE, BENZOYL PEROXIDE, AND ETOFENAMATE

Using udders from slaughtered cows as a new in vitro model of percutan eous drug absorption, the tissue viability and the percutaneous absorp tion of dexamethasone, benzoyl peroxide, and etofenamate were studied. The organ was perfused with gassed tyrode solution for up to 6 hr. As shown by measurement of glucose consumption, lactate production, lact ate dehydrogenase activity, and pH in the perfusate, the tissue was vi able over a 6-hr period. This was confirmed by a histological examinat ion. Determination of the udder skin-fold thickness demonstrated that no edema developed within the perfusion period. A maximum skin penetra tion of dexamethasone was found after administration of dexamethasone dissolved in acetone with dimethyl sulfoxide, followed by ointment wit h salicylic acid, ointment without salicylic acid, and acetone solutio n. Experiments with benzoyl peroxide and etofenamate demonstrated that the perfused udder skin was capable of metabolizing drugs in vitro. I n conclusion, the isolated perfused bovine udder is a new in vitro mod el, which maintains bovine udder skin with an isolated vasculature in a viable state. Using this in vitro model, we note it is possible to c ompare the dermal penetration, metabolism, and absorption of substance s after topical administration of different drug formulations.