ld be taken without regard to meals.
*megestrol acetate oral suspension
Table 1 - Pharmacokinetic Studies Conducted with Megace® ES
Amount Dosed 150 mg 250 mg 375 mg 450 mg 575 mg 625 mg 675 mg 800 mg*
Dose 5 mL 5 mL 5 mL 5 mL 5 mL 5 mL 5 mL 20 mL
Fast Fed Fast Fed Fast Fed Fast Fed Fast Fed Fast Fed Fast Fed Fast Fed
Cmax (ng/mL) 412 379 647 588 810 958 955 1079 - 1421 1133 1618 1044 1616 187 1364
AUC0-∞ (ng∙h/mL) 3058 3889 5194 6328 7238 12193 9483 11800 - 14743 12095 16268 11879 17029 8942 18625
Tmax (h) 1.74 3.80 1.58 3.38 1.56 3.42 1.74 3.16 - 3.75 1.72 2.91 1.96 2.76 5.89 3.85
Plasma steady state pharmacokinetics of megestrol acetate were eva luated in 10 adult, cachectic male patients with acquired immunodeficiency syndrome (AIDS) and an involuntary weight loss greater than 10% of baseline. Patients received single oral doses of 800 mg/day of megestrol acetate oral suspension for 21 days. Plasma concentration data obtained on day 21 were eva luated for up to 48 hours past the last dose.
Mean (±1SD) peak plasma concentration (Cmax) of megestrol acetate was 753 (±539) ng/mL. Mean area under the concentration time-curve (AUC) was 10476 (±7788) ng x hr/mL. Median Tmax value was five hours. Seven of 10 patients gained weight in three weeks.
Additionally, 24 adult, asymptomatic HIV seropositive male subjects were dosed once daily with 750 mg of megestrol acetate oral suspension. The treatment was administered for 14 days. Mean Cmax and AUC values were 490 (±238) ng/mL and 6779 (±3048) hr x ng/mL, respectively. The median Tmax value was three hours. The mean Cmax value was 202 (±101) ng/mL. The mean % of fluctuation value was 107 (±40).
Metabolism
Megestrol acetate metabolites which were identified in urine constituted 5% to 8% of the dose administered. Respiratory excretion as labeled carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine and feces.
Elimination
The major route of drug elimination in humans is urine. When radiolabeled megestrol acetate was administered to humans in doses of 4 to 90 mg, the urinary excretion within 10 days ranged from 56.5% to 78.4% (mean 66.4%) and fecal excretion ranged from 7.7% to 30.3% (mean 19.8%). The total recovered radioactivity varied between 83.1% and 94.7% (mean 86.2%).
Special Populations
The pharmacokinetics of megestrol acetate has not been studied in any special populations.
ANIMAL PHARMACOLOGY AND/OR TOXICOLOGY
Long-term treatment with Megace ® ES (megestrol acetate) may increase the risk of respiratory infections. A trend toward increased frequency of respiratory infections, decreased lymphocyte counts and increased neutrophil counts was observed in a two-year chronic toxicity/carcinogenicity study of megestrol acetate conducted in rats.
DESCRIPTION OF CLIN |
