Pharmacodynamics (21(
S)-hydroxyl-promegestone), the major
active metabolite of promegestone. Promegestone is a
progestogen, or an
agonist of the
progesterone receptor. It has about 200% of the
affinity of
progesterone for the PR. In addition, promegestone has been found to possess some
neurosteroid activity by acting as a
non-competitive antagonist of the
nicotinic acetylcholine receptor, similarly to progesterone.
Pharmacokinetics Following
oral administration,
peak serum levels of promegestone are reached after 1 to 2 hours. The
metabolism of promegestone is mainly via
hydroxylation at the C21 position and at other positions. The medication is
stereoselectively metabolized into
trimegestone, the 21(
S)-hydroxy
metabolite, which is the main compound found in
plasma; it circulates at levels approximately twice those of promegestone itself. A second metabolite, 21(
R)-hydroxypromegestone, circulates at far lower concentrations ( ratio for the (
S)- and (
R)-
isomers of about 21). The
elimination half-life of trimegestone is 13.8 to 15.6 hours. Promegestone, trimegestone, and 21(
R)-hydroxypromegestone are not
excreted in
urine, while 3% of a dose is recovered as the
glucuronide and/or
sulfate conjugate of trimegestone and 1% of a dose is recovered as the glucuronide and/or sulfate conjugate of 21(
R)-hydroxypromegestone. ==Chemistry==