DOXORUBICIN ENCAPSULATED IN LIPOSOMES CONTAINING SURFACE-FOUND POLYETHYLENE-GLYCOL - PHARMACOKINETICS, TUMOR-LOCALIZATION, AND SAFETY IN PATIENTS WITH AIDS-RELATED KAPOSIS-SARCOMA

A study of the plasma pharmacokinetics, tumor localization, and safety of a single dose of doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol (PEG-liposomal doxorubicin) was cond ucted in patients with Kaposi's sarcoma (KS) as a manifestation of acq uired immune deficiency syndrome (AIDS). Eighteen patients with AIDS-K S diagnosed by examination of biopsy specimens were randomly assigned to receive either standard doxorubicin or PEG-liposomal doxorubicin. C onsecutive participants were entered at three dose levels (10, 20, and 40 mg/m(2)) in ascending fashion. Clearance of PEG-liposomal doxorubi cin was 0.034 L/h/m(2) to 0.108 L/h/m(2), volume of distribution (Vd) was 2.2 L/m(2) to 4.4 L/m(2), and half-lives (t1/2) of the initial dec line in the plasma concentration-time curve and of the terminal declin e were 3.77 hours and 41.3 hours, respectively. Seventy-two hours afte r administration, doxorubicin levels observed in lesions of patients r eceiving PEG-liposomal doxorubicin were 5.2 to 11.4 times greater than those found in patients given comparable doses of standard doxorubici n. PEG-liposomal doxorubicin and standard doxorubicin were roughly equ ipotent in producing toxicity, Encapsulation in liposomes containing s urface-bound PEG significantly limits the distribution and elimination of doxorubicin, results in greater accumulation of the drug in KS les ions 72 hours after dosing than does standard doxorubicin, and may imp rove drug efficacy and therapeutic index in the treatment of AIDS-KS.