A rabbit ear flap perfusion experiment to evaluate the percutaneous absorption of drugs

A rabbit ear flap single-pass perfusion system was examined as an experimental method for studying the relationship between the physiological conditions of tissues and drug disposition after topical applications. Tyrode solutions containing bovine serum albumin (BSA) and sucrose or flurbiprofen (FP), used as a model drug, were perfused through the vessel in the ear flap to evaluate the physiological conditions prior to the application of FP to the skin surface. The extracellular volume and distribution properties of FP in the perfused ear were similar to those in an in vivo experimental system. In addition, the perfused ear flap exhibited a pharmacological response to bradykinin (BK). The amount of FP in the outflow Tyrode solution containing BSA after application to the skin surface of the perfused ear decreased with the addition of BK, while that in the tissues under the application site increased. FP binds to BSA, which leaked from the intravascular space, and could be retained in the tissues under the application site. The protein binding also affected the redistribution of FP to other tissues in the ear flap after application to the skin. The rabbit ear perfusion system is a useful method for studying the percutaneous absorption of drugs especially variations in the disposition of drugs in oedematous tissues.