A comparative pharmacokinetic study of micronized estradiol valerate administered alone and in combination with medroxyprogesterone acetate in postmenopausal women

Abstract

The objective of this study was to evaluate a possible pharmacokinetic interaction between 17beta-estradiol (E-2) and medroxyprogesterone (MP) when administered together in a combined tablet because both hormones have common metabolic routes of biotransformation. The study assessed the mean pharmacokinetics parameters of E2 found after 1-dose administration of 2 different tablets containing E-2, 1 containing 2 mg of micronized 17beta-estradiol valerate (E2V) and the other, administered after 2 weeks, 2 mg of E,V in combination with 5 mg of medroxyprogesterone acetate (MPA). The subjects were 15 healthy postmenopausal women with normal laboratory and clinic tests. The study was randomized, double blind, crossover, with 2 periods and 2 sequences. The blood samples were obtained at 0, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after each administration. The F, serum concentrations were determined by electrochemoluminiscence assay. From these data, the following pharmacokinetic parameters were calculated for E, alone and E, in combination with MPA (E2V/MPA): C-max = 104.89 +/- 26.96, 103.27 +/- 44.40; AUC(0-24) = 1900.30 +/- 392.23, 1783.70 +/- 756.39; AUC(0-infinity) = 5576.06 +/- 4065.87, 5317.89 +/- 3702.54; k(a) = 1.06 +/- 0.31, 1.09 +/- 0.13; t1/2 = 35.65 +/- 20.62, 36.12 +/- 18.04; MRT = 16.29 +/- 8.77,16.27 +/- 4.88; V/F = 16.29 +/- 8.76, 16.27 +/- 4.88. No significant differences between the pharmacokinetic parameters of E-2 and E-2/MPA were found, which led us to conclude that there is no pharmacokinetic interaction.