THE SAFETY AND PHARMACOKINETICS OF SINGLE-AGENT AND COMBINATION THERAPY WITH MEGESTROL-ACETATE AND DRONABINOL FOR THE TREATMENT OF HIV WASTING SYNDROME

This randomized, open-labeled, multicenter study was designed to asses s safety and pharmacokinetics of dronabinol (Marinol) tablets and mege strol acetate (Megace) micronized tablets, alone and in combination, f or treatment of HIV wasting syndrome, Weight and quality of life data were also collected, Fifty-two patients (mean CD4(+) count, 59 cells/m u l) were randomized to one of four treatment arms: dronabinol 2.5 mg twice/day (D); megestrol acetate 750 mg/day (M750); megestrol acetate 750 mg/day+dronabinol 2.5 mg twice/day (R4750+D); or megestrol acetate 250 mg/day+dronabinol 2.5 mg twice/day (M250+D), After therapy initia tion, 47 patients returned for at least one visit, and 39 completed th e planned 12 weeks of study visits, Occurrence of adverse events, drug discontinuation, new AIDS-defining conditions, or CD4(+) T lymphocyte changes were not statistically significantly different among arms, Se rious adverse events assessed as related to dronabinol included CNS ev ents (e.g., confusion, anxiety, emotional lability, euphoria, hallucin ations) and those assessed as related to megestrol acetate included dy spnea, liver enzyme changes, and hyperglycemia. The mean weight change +/- SE over 12 weeks was as follows: D, -2.0 +/- 1.3 kg; M750, +6.5 /- 1.1 kg; M750+D, +6.0 +/- 1.0 kg; and M250+D, -0.3 +/- 1.0 kg (diffe rence among treatment arms, p = 0.0001), Pharmacokinetic parameters me asured after 2 weeks of therapy for M750 were C-max = 985 ng/ml and AU C = 22,487 ng x hr/ml, and for dronabinol and its active metabolite (H O-THC), respectively, were C-max = 2.01; 4.61 ng/ml and AUC = 5.3; 23. 7 ng x hr/ml, For megestrol acetate, but not dronabinol, there was a p ositive correlation at week 2 between both C-max and AUC with each of the following: (1) weight change, (2) breakfast visual analog scale fo r hunger (VASH) score, and (3) dinner VASH score.