Absorption, Distribution and Excretion
Absorption of 17-hydroxyprogesteron caproate is slow, occurring over a long period of time.
Following intramuscular injection, approximately 50% of hydroxyprogesterone caproate metabolites are eliminated in the feces, while approximately 30% of metabolites are eliminated in the urine.
Hydroxyprogesterone caproate has a high volume of distribution.
Clearance is highly variable from patient to patient.

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Metabolism / Metabolites
The main enzymes involved in metabolism of hydroxyprogesterone caproate are cytochrome P450 (CYP) 3A4 and to a lesser extent CYP3A5.

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Biological Half-Life
Half-life = 16 days (±6 days).

Protein Binding
Hydroxyprogesterone caproate is extensively protein bound in the plasma.

Hydroxyprogesterone caproate is a corticosteroid hormone.
Hydroxyprogesterone caproate is a synthetic steroid hormone that is similar to medroxyprogesterone acetate and megestrol acetate. It is an ester derivative of 17α-hydroxyprogesterone formed from caproic acid (hexanoic acid). Hydroxyprogesterone caproate was previously marketed under the trade name Delalutin by Squibb, which was approved by the U.S. Food and Drug Administration (FDA) in 1956 and withdrawn from marketing in 1999. The U.S. FDA approved Makena from KV Pharmaceutical (previously named as Gestiva) on February 4, 2011 for prevention of preterm delivery in women with a history of preterm delivery, sparking a pricing controversy. In April 2023, the FDA withdrew its approval of Makena and its generics given an unfavorable risk-to-benefit assessment.
Hydroxyprogesterone Caproate is a synthetic progestational agent similar to the endogenous progesterone used in hormone therapy or as a female contraceptive. Mimicking the action of progesterone, hydroxyprogesterone caporate binds to and activates nuclear progesterone receptors in the reproductive system and causes the ligand-receptor complex to be translocated to the nucleus where it binds to and promotes expression of target genes. Due to the negative feedback mechanism seen with progesterone, this agent also blocks luteinizing hormone (LH) release from the pituitary gland, thereby leading to an inhibition of ovulation and an alteration in the cervical mucus and endometrium. Furthermore, without stimulation of LH, estrogen release from the ovaries is stopped, hence impeding the growth of estrogen-sensitive tumor cells.
17α-Hydroxyprogesterone caproate is a synthetic steroid hormone that is similar to medroxyprogesterone acetate and megestrol acetate. It is an ester derivative of 17α-hydroxyprogesterone formed from caproic acid (hexanoic acid). 17α-Hydroxyprogesterone caproate was previously marketed under the trade name Delalutin by Squibb, which was approved by the U.S. Food and Drug Administration (FDA) in 1956 and withdrawn from marketing in 1999. Cytyc is seeking FDA approval to market 17α-hydroxyprogesterone caproate under the trade name Gestiva for prevention of preterm delivery in women with a history of preterm delivery. [Wikipedia]
Hydroxyprogesterone derivative that acts as a PROGESTIN and is used to reduce the risk of recurrent MISCARRIAGE and of PREMATURE BIRTH. It is also used in combination with ESTROGEN in the management of MENSTRUATION DISORDERS.
See also: Hydroxyprogesterone (has active moiety).

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Drug Indication
Hydroxyprogesterone caproate was previously indicated in the US for the prevention of spontaneous preterm births in singleton pregnancies in women with a history of spontaneous preterm birth. This indication was revoked by the FDA in April 2023. Hydroxyprogesterone caproate remains indicated in other jurisdictions for the management of primary and secondary amenorrhea, corpus luteum insufficiency, and for the prevention of preterm birth.
FDA Label

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Mechanism of Action
The mechanism by which progesterone prevents preterm birth is not well understood, but many pathways are likely involved. Progesterone plays a vital role in regulation of the female reproductive system and is important for successful implantation of the embryo and maintenance of pregnancy. It acts by binding to progesterone receptors in the uterus, ovaries, breasts and in the central nervous system. These receptors exist in 2 isoforms, PR-A and PR-B. Progesterone binding to these receptors ultimately leads to regulation of gene transcription. This results in an anti-inflammatory effect which blunts the proinflammatory state that occurs with initiation of labor, and maintains uterine queiscence by stabilizing progesterone acting on the myometrium.

C27H40O4

428.61

428.292

630-56-8

169870

White to off-white solid powder

1.1±0.1 g/cm3

540.0±50.0 °C at 760 mmHg

119°C

229.2±30.2 °C

0.0±1.4 mmHg at 25°C

1.532

5.53

0

4

7

31

797

6

O(C(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])=O)[C@]1(C(C([H])([H])[H])=O)C([H])([H])C([H])([H])[C@@]2([H])[C@]3([H])C([H])([H])C([H])([H])C4=C([H])C(C([H])([H])C([H])([H])[C@]4(C([H])([H])[H])[C@@]3([H])C([H])([H])C([H])([H])[C@@]21C([H])([H])[H])=O

DOMWKUIIPQCAJU-LJHIYBGHSA-N

InChI=1S/C27H40O4/c1-5-6-7-8-24(30)31-27(18(2)28)16-13-23-21-10-9-19-17-20(29)11-14-25(19,3)22(21)12-15-26(23,27)4/h17,21-23H,5-16H2,1-4H3/t21-,22+,23+,25+,26+,27+/m1/s1

[(8R,9S,10R,13S,14S,17R)-17-acetyl-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] hexanoate

Idrogestene; Delalutin; 17-((1-Oxohexyl)oxy)pregn-4-ene-3,20-dione

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~25 mg/mL (~58.33 mM)
H2O : ~0.1 mg/mL (~0.23 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (5.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)