Evaluation of two new megestrol acetate tablet formulations in humans

Abstract

The bioequivalence of two new investigational 160 mg tablets, one containing the regular form and the other a micronized form of megestrol acetate, was determined relative to a commercially available 40 mg tablet (Megace). The tablets were administered to 24 male subjects in a three-way cross-over study, balanced for sequence, with a week between administrations. The 40 mg tablets were administered q.i.d. at 08.00, 12.00, 18.00 and 22.00 h, while the 160 mg tablets were administered once at 08.00 h. Plasma samples were collected at appropriate times out to 96 h after administration and were analysed for megestrol acetate with a validated high performance liquid chromatographic procedure. Based on the times to maximum plasma concentrations (2.5 to 2.8 h), the absorption rate constant was the same for each of the tablets. Relative to the 40 mg q.i.d. dose, the 160 mg regular and the 160 mg micronized tablets had mean relative bioavailabilities of 97 per cent and 118 per cent, respectively.

Clinical Pharmacokinetics of Endocrine Agents Used in Advanced Breast Cancer

“…Plasma AUC values after single medroxyprogesterone 1000mg doses or megestrol 160mg were 230 to 900 JLg/L • hand 1860 to 2425 JLg/L· h, respectively (Gaver et al 1985;Pannuti et al 1982;Stockdale et al 1987). Medroxyprogesterone is slightly bound to albumin and does not bind specifically to other plasma proteins (Mathrubutham & Fotherby 1981).…”

Progesterone pharmacokinetics in the mouse: implications for potential stroke therapy

“…Progesterone has advantages compared with oestrogen in terms of reduced side‐effects in males and a better safety profile, for example there is a lower incidence of breast cancer associated with exogenous progesterone [19] . Also, no severe adverse effects have been associated with high progesterone doses in transient use [20,21] . Progesterone has already been shown to be safe and effective for many other clinical applications, for example hormone replacement therapy and a variety of preparations are available for different modes of administration [22] .…”

Megestrol acetate: Phase II study of a single daily administration in advanced breast cancer

“…Most studies have employed a dose of 40 mg of megestrol acetate per os four times daily; recently, however, a single administration of 160mg has been shown to have equal bioavailability [7]. Carpenter et al [15] treated twenty patients with 160 mg of megestrol acetate in a single daily admin- istration, obtaining encouraging results.…”

“…Recently, a new formulation of megestrol acetate in 160 mg tablets, allowing single daily administration, has been shown to deliver the same amount of total drug to plasma as the standard 40 mg q.i.d, regimen [7].…”