Pharmacokinetics and metabolism of medroxyprogesterone acetate in patients with advanced breast cancer.

The pharmacokinetics and metabolism of medroxyprogesterone acetate (MPA) were studied in patients with advanced breast cancer after i.v. injection and oral administration of [3H]MPA. MPA was distributed very rapidly into three compartments after i.v. injections, revealing half-lives of 4-7 h. Using a nonlinear model fitting metabolic clearance rates (MCR) were found to be 652 1/day before and 601 1/day during MPA treatment, and distribution volumes (V0) 5.9 and 3.41 respectively. The major metabolite of MPA following i.v. injection was a glucuronide of MPA, presumably of the 3-enol form. After oral administration the radioactivity in serum increased rapidly and reached a plateau of about 1% of the dose per litre serum after approx 2 h. About 80-90% of the radioactivity was found in the water phase after hexane extraction, persumably as glucuronides of metabolites more polar than MPA. Radioimmunoassay (RIA) of MPA in untreated serum samples showed 3-8-fold greater MPA values as compared to measurements in hexane extracts of serum. Ethanol extraction did not remove these interfering substances. Extraction of serum with a low polar solvent before RIA of MPA is essential in order to prevent great overestimation, as the glucuronidated polar metabolites most likely will crossreact in an assay with an antiserum raised against a MPA-3-O-carboximethyloxime coupled to bovine serum albumin.