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

✍ Scribed by Dr D. Smith; R. Enever; M. Dey; D. Latta; R. Weierstall

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 631 KB
• Volume: 14
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510140407

✦ Synopsis

Medroxyprogesterone acetate (MPA) has been administered to rats and dogs. Dogs received single oral doses of 2.5, 5, and lOmg 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-I 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,, 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.