Clinical pharmacokinetics of mitoxantrone in hyperthermic,isolated perfusion of the leg

Summary The clinical pharmacokinetics of mitoxantrone in hyperthermic, isolated perfusion of the leg were studied in five patients exhibiting solitary, localized malignant melanoma. Mitoxantrone was given as four 1-min infusions at 15-min intervals into the arterial line of the perfusion system at a total dose of up to 14 mg/m². The mean half-lives for mitoxantrone in the blood circulation of the leg were:t_1/2 (distribution phase), 25.5 s, andt_1/2 (elimination phase), 14.9 min. The mean volume of distribution at steady state in the leg was 25.6 l. In the arterial part of the perfusion, the mean AUC was 155.9 mg min l^–1, and that in the corresponding venous part was 91.6 mg min l^–1. Leakage of the drug from the leg into the systemic circulation amounted to 1.2% of the total delivered dose; 91% of the delivered dose remained in the leg after the perfusion had been completed. The mean elimination half-life of mitoxantrone in the systemic circulation was 123 min and the corresponding AUC for systemic concentrations was 8.59 mg min l^–1. The present data revealed a high uptake of mitoxantrone into the leg and low systemic drug concentrations due to minor leakage, suggesting that mitoxantrone might be a good candidate for use in isolated, hyperthermic limb perfusion.