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Pharmacokinetic study of low- versus high-dose medroxyprogesterone acetate (MPA) in women
Authors:Tomoko Ohtsu  Hirofumi Fujii  Hisashi Wakita  Tadahiko Igarashi  Kuniaki Itoh  Shigeru Imoto  Masahiro Kohagura  Yasutsuna Sasaki
Affiliation:(1) Division of Oncology/Hematology, Department of Medicine, and Division of Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277, Japan (TEL) +81-(0)471-33-1111, (FAX) +81-(0)471-31-4724, JP;(2) Kyowa Analytical Research Center, 1188 Shimotogari, Nagaizumi, Suntogun, Shizuoka 411, Japan, JP
Abstract:The present study was conducted to compare the pharmacokinetics (PK) of low-dose versus high-dose medroxyprogesterone (MPA) as a once-daily oral administration. Of 32 patients, all women, enrolled in this PK study, 18 received 600 mg MPA daily and 14 received 1200 mg daily. Detailed 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 concentration (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. Five patients demonstrated extremely low AUC and Cmax (<10 ng/ml) values on day 1. Phenobarbital, dexamethasone and betamethasone were being taken concomitantly with the MPA each by one patient. The serum MPA concentrations were markedly increased after the discontinuation of phenobarbital in that patient, suggesting a drug interaction. At present we cannot recommend the high dose of MPA, except in clinical studies, from a PK or a pharmacodynamic points of view. Received: 2 May 1997 / Accepted: 13 October 1997
Keywords:Pharmacokinetics  MPA  Drug-to-drug interaction
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