Medroxyprogesterone Acetate Pharmacokinetics Following Oral High‐Dose Administration in Humans: A Bioavailability Evaluation of a New MPA Tablet Formulation

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Abstract
The pharmacokinetics of medroxyprogesterone acetate (MPA) in healthy female volunteers have been investigated following oral administration of single doses of six different high-dose MPA tablet formulations. Blood samples were obtained over 96 hrs following administration. The plasma was separated and analyzed in duplicate for MPA by radioimmunoassay (RIA) after extraction with petroleum ether. A two compartment open model with first order absorption was computer-fitted to the plasma concentration of MPA. Following oral administration MPA is rapidly transferred from the gastrointestinal tract to the blood circulation with a half-life of the absorption process of 15-30 min. The peak plasma concentration is reached 1-3 hrs after administration, and the biological half-life of MPA is 40-60 hrs. Following administration of 1000 mg MPA the areas under the plasma concentration-time curves .**GRAPHIC**. were calculated to (mean and S.E.): 3357 (438) nmol/l and 2403 (245) nmol/l for Leo formulation A and Farlutal, respectively (P < 0.02). Following administration of 500 mg the areas were: 2325 (389) nmol/l, 1793 (312) nmol/l, 1778 (239) nmol/l, 1178 (209) nmol/l, and 556 (89) nmol/l for Gestapuran, Leo formulation A (P = n.s.), Leo formulation B (P = n.s.), Provera (P < 0.001), and Lutopolar (P < 0.001), respectively. The in vitro dissolution rates of MPA from the tablet formulations were determined and compared with the results of the bioavailability studies, indicating that a rapid dissolution rate as well as the particle size of MPA are two important factors to ensure optimal absorption of MPA from the gastrointestinal tract.