Definition of a Physiologic Pharmacokinetic Model of Cutaneous Drug Distribution Using the Isolated Perfused Porcine Skin Flap

A physiologic pharmacokinetic model describing drug disposition in the isolated perfused porcine skin flap (IPPSF) is derived. The IPPSF is well suited for experimental studies of dynamic drug distribution into skin because arterial and venous drug fluxes can be continuously monitored. The system parameters of the model are uniquely identifiable and describe the cutaneous efflux profile as a function of arterial input flux and tissue partitioning or extraction. This model allows experimental results obtained from an in vitro preparation to serve as a quantitative input to an in vivo, whole animal pharmacokinetic system. Experimental infusion applications of the cancer chemotherapeutic agents cisplatin and carboplatin and the antimicrobials tetracycline and doxycycline are reported herein.