Chemical formula: C₂₁H₂₈O₂ Molecular mass: 312.446 g/mol PubChem compound: 9051
Dydrogesterone is an orally-active progestogen having an activity comparable to parenterally administered progesterone.
As oestrogens promote the growth of the endometrium, unopposed oestrogens increase the risk of endometrial hyperplasia and cancer. The addition of a progestogen greatly reduces the oestrogen-induced risk of endometrial hyperplasia in non-hysterectomised women.
Following oral administration, dydrogesterone is rapidly absorbed with a Tmax between 0.5 and 2.5 hours. The absolute bioavailability of dydrogesterone (oral 20 mg dose versus 7.8 mg intravenous infusion) is 28%.
The following table provides the mean steady state pharmacokinetic parameters of dydrogesterone (D) and dihydrodydrogesterone (DHD). Data is presented as mean (SD).
Dydrogesterone 2.5 mg:
| Parameters | D | DHD |
|---|---|---|
| Cmax (ng/mL) | 0.759 (0.313) | 18.9 (7.22) |
| Cmin (ng/mL) | 0.0309 (0.0209) | - |
| Cav (ng/mL) | 0.117 (0.0455) | - |
| AUC0-τ (ng.h/mL) | 2.81 (1.09) | 90.4 (44.1) |
After intravenous administration of dydrogesterone the steady-state volume of distribution is approximately 1400 L. Dydrogesterone and DHD are more than 90% bound to plasma proteins.
Following oral administration, dydrogesterone is rapidly metabolised to DHD. The levels of the main active metabolite 20 α-dihydrodydrogesterone (DHD) peak about 1.5 hours postdose. The plasma levels of DHD are substantially higher as compared to the parent drug. The AUC and Cmax ratios of DHD to dydrogesterone are in the order of 40 and 25, respectively. Mean terminal half lives of dydrogesterone and DHD vary between 5 to 7 and 14 to 17 hours, respectively. A common feature of all metabolites characterised is the retention of the 4,6 diene-3-one configuration of the parent compound and the absence of 17α-hydroxylation. This explains the lack of oestrogenic and androgenic effects of dydrogesterone.
After oral administration of labelled dydrogesterone, on average 63% of the dose is excreted into the urine. Total plasma clearance is 6.4 L/min. Within 72 hours excretion is complete. DHD is present in the urine predominantly as the glucuronic acid conjugate.
The single and multiple dose pharmacokinetics are linear in the oral dose range 2.5 to 10 mg. Comparison of the single and multiple dose kinetics shows that the pharmacokinetics of dydrogesterone and DHD are not changed as a result of repeated dosing. Steady state was reached after 3 days of treatment.
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