Pharmacokinetics (PK), tumor localization (TL), and safety of Doxil (liposomal doxorubicin) in AIDS patients with Kaposi's sarcoma (AIDS-KS) (Meeting abstract).

Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

Pharmacokinetics (PK), tumor localization (TL), and safety of Doxil (liposomal doxorubicin) in AIDS patients with Kaposi's sarcoma (AIDS-KS) (Meeting abstract).

Proc Annu Meet Am Soc Clin Oncol; 12:A8 1993. Unique Identifier : AIDSLINE ICDB/93694408
Northfelt DW; Martin FJ; Kaplan LD; Russell J; Anderson M; Lang J; Volberding PA; AIDS Program, Univ. of California, San Francisco, CA 94143

Abstract: Objectives: To compare the PK, TL, and safety of comparable single doses of Adriamycin (A) and Doxil in patients with AIDS-KS. Methods: Subjects with AIDS-KS were prospectively randomized to receive a single dose of either A or Doxil, 6 subjects at 10 mg/m2, 6 at 20 mg/m2, and 4 at 40 mg/m2. Plasma drug levels were measured at various time points up to 4 days after dosing. At 72 hr after dosing, an AIDS-KS skin lesion was excised from each subject and the tissue drug level determined. Safety was assessed weekly for 4 wk after dosing. Results: Mean distribution T1/2 for Doxil at 10, 20, and 40 mg/m2 was 41.1, 43.5, and 33.3 hr, respectively. T1/2 for A at all dose levels was less than 10 min. Area under the curve (AUC) for Doxil was 151, 277, and 580 mg hr/L at the doses studied. Tumor doxorubicin levels at 72 hr were 2.06, 1.61, and 7.11 ug drug/g of tissue in Doxil-treated subjects at the doses studied; corresponding levels in the A-treated subjects were 0.18, 0.31, and 0.72. Doxil was well-tolerated by all subjects; the most frequent and severe adverse effects were hematologic toxicities, most notably leukopenia and neutropenia. The safety of Doxil was found to be similar to that of A at similar doses. Conclusions: Plasma PK of Doxil is dramatically different from that of A, with a 300-fold increase in T1/2 and a 100- to 200-fold increase in AUC. Moreover, on a dose-equivalent basis, Doxil delivers 5- to 11-fold more doxorubicin to AIDS-KS lesions than standard A therapy. Doxil is well-tolerated by patients with AIDS-KS, with safety similar to similar doses of A.

Keywords: Acquired Immunodeficiency Syndrome/BLOOD/DRUG THERAPY Comparative Study Doxorubicin/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/ *PHARMACOKINETICS Drug Carriers Half-Life Human Liposomes Metabolic Clearance Rate Prospective Studies Sarcoma, Kaposi's/*BLOOD/DRUG THERAPY Skin Neoplasms/*BLOOD/DRUG THERAPY ABSTRACT CLINICAL TRIAL RANDOMIZED CONTROLLED TRIAL
931230
M93C0819

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