Abstract

The aim of this study was to determine whether short term replacement therapy with estradiol and norethisterone affect the pharmacokinetics of phenazone. The study group comprised of 10 women, aged between 38-62 years, at least six weeks following ovariectomy. Each patient received estradiol (transdermally, 4 mg plaster every 3 days) for a period of 18 days, and subsequently norethisterone (orally, 5 mg per day) for 10 days, with an interval of one day. Pharmacokinetic studies were performed 3 times: prior to estradiol administration, on the last day of estradiol treatment and on the last day of norethisterone administration. Pharmacokinetic assays were performed following a single, oral administration of phenazone at a dose of 1.0 g, followed by blood sampling fora period of 24 hours, in order to determine plasma phenazone concentration levels. Brodi's method was applied for the measurement of phenazone concentrations. The one-compartment open model for extravascular administration was used for the calculations of pharmacokinetic parameters. Short-term administration of estradiol did not significantly alter pharmacokinetic parameter valuess determined during the study. Hormonal replacement therapy with norethisterone does not modify the pharmacokinetics of phenazone. Hormonal replacement therapy with both estradiol and norethisterone does not affect the biotransformation of phenazone.

Keywords: phenazone pharmacokinetics, norethisterone, Estradiol, hormonal replacement therapy