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 C(max) 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.