Pharmacokinetics of two different delivery regimens of doxorubicin in isolated hyperthermic limb perfusion

Evaluation of doxorubicin (DOX) pharmacokinetics in hyperthermic isolated limb perfusion (HILP) is limited. In this study two administration regimens of DOX were compared in terms of area under the time concentration curve (AUC) in plasma. HILP was performed in 13 dogs. In group 1 (n = 7) four single doses of DOX were injected in intervals of 15 minutes, in group 2 (n = 6) DOX was administered continuously during the first 30 min. The total dose in both groups was 1 mg/kg body weight, and the perfusion lasted 60 min. Concentrations of DOX and its major metabolite doxorubicinol (DOXol) were measured in perfusate and muscle tissue by high performance liquid chromatography (HPLC). Pharmacokinetic estimates were calculated. The two investigated administration modes provided sufficient drug levels of DOX during the whole perfusion time. Maximum concentrations in the perfusate and areas under the time concentration curves were nearly the same. The tissue concentrations also did not show significant differences. Both regimens are practicable avoiding high peak levels of the drug in order to minimize toxic side effects.