Dydrogesterone - Pharmacokinetics

Pharmacokinetics

Dydrogesterone is readily absorbed after oral administration. T_max values vary between 0.5 and 2.5 hours.

Metabolisation of dydrogesterone is virtually complete. The main metabolic reaction is hydrogenation of the 20-keto group, resulting in 20-dihydrodydrogesterone (DHD), another potent progestogen. The levels of the main active metabolite DHD also peak about 1.5 hours after dosing.

After oral administration, plasma concentrations of DHD are substantially higher than those of the parent drug. The ratios of DHD/Dydrogesterone for AUC and C_max are in the order of 40 and 25, respectively. Absolute bio-availability is on average 28%.

All the metabolites of dydrogesterone retain the 4, 6-diene-3-one structure, and are metabolically stable. As such, dydrogesterone does not undergo aromatisation, which is consistent with its absence of estrogenic effects. Furthermore, dydrogesterone does not undergo 17α-hydroxylation, which explains its lack of androgenic effects.

Dydrogesterone has predictable pharmacokinetics. The single-dose kinetics are linear in the oral dose range of 5–20 mg. The pharmacokinetics do not change during repeated administration of up to 20 mg dydrogesterone once daily. Steady state is attained after 3 days of treatment.

Dydrogesterone and its metabolites are excreted predominantly in urine. About 85% of an oral dose is excreted within 24 hours. The mean terminal half-lives od dydrogesterone and DHD vary between 5-7 and 14–17 hours, respectively.

In HRT, dydrogesterone is administered together with an estrogen. Therefore, the interaction between dydrogesterone and estrogens has been assessed, and no clinically significant interaction has been observed.