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Pharmacology: Pharmacokinetics: Absorption: After oral administration Dydrogesterone is rapidly absorbed with a Tmax of between 0.5 and 2.5 hours. The absolute biological availability of Dydrogesterone (20 mg oral dose versus 7.8 mg intravenous infusion) is 28%.
Distribution: After intravenous administration of Dydrogesterone the steady-state distribution volume is around 1400 L. More than 90% of Dydrogesterone and 20α-dihydrodydrogesterone (DHD) are bound to plasma-proteins.
Metabolism: After oral administration Dydrogesterone is quickly metabolised to DHD. The plasma levels of the main active metabolite DHD show a peak around 1.5 hours after administering the dose. The plasma levels of DHD are substantially higher than the related medicinal product. The AUC and Cmax ratios of DHD and Dydrogesterone are of the order of magnitude of respectively 40 and 25. The mean terminal half-life of Dydrogesterone and DHD varies from respectively 5 to 7 and 14 to 17 hours. A common characteristic of all characterized metabolite is the retention of the 4, 6-diene-3-one configuration of the original product and the absence of 17α-hydroxylation. This explains the absence of oestrogenic and androgenic effects of Dydrogesterone.
Elimination: After oral administration of labeled Dydrogesterone on average 63% of the dose is excreted in the urine. The total plasma clearance is 6.4 L/minute. Within 72 hours the excretion is complete, DHD is present in the urine mainly as the conjugated glucuronic acid.
Dependence of dose and time: The pharmacokinetics of single and multiple doses are linear in the oral dosage range from 2.5 to 10 mg. Comparison of the kinetics of single and multiple doses shows that the pharmacokinetics of Dydrogesterone and DHD do not change as a result of repeated dosing. Steady state is reached after 3 days of treatment.
