Effect of hyperthermia on cisplatin (CDDP) disposition to isolated perfused skin

Hyperthermia has previously been postulated to enhance tissue uptake of systemically administered chemotherapeutic drugs. Normothermic (36.2 degrees C) and hyperthermic (42.1 degrees C) isolated perfused porcine skin flaps (IPPSF) were infused with cisplatin (CDDP) to assess any influence of heat on drug disposition to skin. A three-compartment physiologically relevant model was employed to interpret kinetically the measured arterial and venous flux profiles. Additionally, non-parametric methods were applied to these data in an effort to confirm the propriety of the model. Results of both approaches suggest that heat does not increase tissue uptake of CDDP after infusion in isolated perfused skin, although it does increase the mobility of CDDP as evidenced by shorter transit times through the IPPSF. These findings are similar to those seen in skin in vivo, but do not predict the enhanced in vivo uptake seen with hyperthermia in more highly perfused tissues.