PHARMACOKINETIC STUDY OF LOW-DOSE VERSUS HIGH-DOSE MEDROXYPROGESTERONE ACETATE (MPA) IN WOMEN

The present study was conducted to compare the pharmacokinetics (PK) o f low-dose versus high-dose medroxyprogesterone (MPA) as a once-daily oral administration. Of 32 patients, all women, enrolled in this PK st udy, 18 received 600 mg MPA daily and 14 received 1200 mg daily. Detai led PK data were obtained on day 1 and after more than 4 weeks of MPA treatment. In addition, multiple data for the minimum steady-state con centration (Css min) were analyzed. The MPA serum concentrations were measured by high-performance liquid chromatography. Wide interpatient variability was found in the PK parameters obtained both on day 1 and after more than 4 weeks. There were no clear relationships between the oral dose and the MPA peak concentration (Cmax), area under the time versus concentration curve (AUC), or mean Css min. Weight gains of 10% or more were demonstrated more frequently in the high-dose group (P < 0.01). Liver dysfunction (n = 5) did not influence the PK of MPA. Fiv e patients demonstrated extremely low AUC and Cmax (<10 ng/ml) values on day 1. Phenobarbital, dexamethasone and betamethasone were being ta ken concomitantly with the MPA each by one patient. The serum MPA conc entrations were markedly increased after the discontinuation of phenob arbital in that patient, suggesting a drug interaction. At present we cannot recommend the high dose of MPA, except in clinical studies, fro m a PK or a pharmacodynamic points of view.