Pharmacokinetics and bioavailability of medroxyprogesterone acetate in the dog and the rat

Medroxyprogesterone acetate (MPA) has been administered to rats and dogs. Dogs received single oral doses of 2.5, 5, and 10 mg MPA and a single intravenous dose of 1 mg MPA. Rats received single oral doses of 0.2, 1, 5, and 20 mg kg-1 MPA and multiple oral doses (14 daily doses) of 0.2, 5, and 20 mg kg-1 MPA. Dog plasma MPA levels from the intravenous dose were characterized by a triexponential decay with disposition half-lives of 0.3, 1.8, and 21.6 h. A Loo-Riegelman analysis of the dog plasma MPA levels from oral doses indicated absorption was not a simple first-order process. The Weibull Function was used to characterize the absorption kinetics of MPA. The oral absorption of MPA in dogs appears to be dose-linear over the dosage range studied, and the absolute bioavailability was estimated at 27 per cent. Rat plasma MPA levels from single and multiple oral doses were analyzed by a non-compartmental approach. AUC and Cmax values were not dose-linear over the dosage range studied; indicative of the self-induced metabolism of MPA. Exposure of similar dosages of MPA to both the rat and the dog resulted in similar plasma profiles and pharmacokinetics.