Hydroxyprogesterone caproate binds to and activates nuclear progesterone receptors in the reproductive system. It exhibits equivalent affinity for progesterone receptor A and progesterone receptor B. The ligand-receptor complex is translocated to the nucleus where it binds to and promotes expression of target genes.

In vitro, Hydroxyprogesterone caproate activates progesterone receptor-mediated gene transcription. It downregulates estrogen receptors in target tissues and activates their metabolic pathways. The compound inhibits ovulation and causes alterations in cervical mucus and endometrium. It exhibits anti-estrogenic, anticancer, and anti-inflammatory properties.

In vivo, Hydroxyprogesterone caproate mimics the action of endogenous progesterone. Due to the negative feedback mechanism seen with progesterone, this agent also blocks luteinizing hormone (LH) release from the pituitary. It has been studied for its ability to reduce the risk of preterm birth in pregnant women at risk. The compound is administered as an intramuscular injection.

In vitro receptor binding assays for Hydroxyprogesterone caproate typically use membrane preparations from cells expressing progesterone receptor A or B. Radiolabeled progesterone is displaced by increasing concentrations of the compound to determine binding affinity (Ki). Non-specific binding is determined in the presence of excess unlabeled progesterone. Bound radioactivity is measured by scintillation counting.

Cell-based functional assays utilize cells transfected with progesterone receptor-responsive reporter genes (e.g., luciferase under a progesterone response element). Cells are treated with varying concentrations of Hydroxyprogesterone caproate, and reporter gene activity is measured after 24-48 hours. EC50 values are calculated from dose-response curves. The compound's ability to modulate estrogen receptor activity can also be assessed.

In vivo animal studies typically involve administration of Hydroxyprogesterone caproate to pregnant rodents or rabbits. The compound is injected intramuscularly at various doses. Effects on pregnancy maintenance, preterm birth prevention, and fetal development are assessed. Plasma progesterone levels are measured by radioimmunoassay. Uterine and cervical changes are evaluated by histology. Efficacy in preventing preterm labor is the primary endpoint.

Absorption, Distribution and Excretion
17-Hydroxyprogesterone caproate is absorbed slowly over a long period. After intramuscular injection, approximately 50% of hydroxyprogesterone caproate metabolites are excreted in feces, and approximately 30% in urine. Hydroxyprogesterone caproate has a large volume of distribution. Clearance varies from person to person. Metabolism/Metabolites The main enzyme involved in the metabolism of hydroxyprogesterone caproate is cytochrome P450 (CYP) 3A4; CYP3A5 has a relatively minor role. Biological Half-Life Half-life = 16 days (±6 days).
Pharmacokinetic properties of Hydroxyprogesterone caproate are characterized by slow release from the intramuscular injection site, providing sustained systemic exposure. The compound has a long half-life, allowing for weekly or biweekly dosing. It is highly protein-bound in circulation and metabolized in the liver. Excretion occurs primarily through renal pathways. The caproate ester prolongs the duration of action compared to unesterified progesterone.

Protein Binding
Hydroxyprogesterone caproate binds extensively to proteins in plasma.
Toxicological profile of Hydroxyprogesterone caproate is well-established from clinical use. Common side effects include injection site reactions, nausea, dizziness, and headache. Rare but serious adverse events include thromboembolic events, jaundice, and depression. The compound is contraindicated in patients with liver disease, breast cancer, or thromboembolic disorders. It has a favorable safety profile when used as indicated.

Hydroxyprogesterone caproate is a corticosteroid hormone. It is a synthetic steroid hormone, similar to medroxyprogesterone acetate and megestrol acetate. It is an ester derivative of 17α-hydroxyprogesterone, derived from hexanoic acid (hexanoic acid). Hydroxyprogesterone caproate was marketed by Bristol-Myers Squibb under the brand name Delalutin and approved by the U.S. Food and Drug Administration (FDA) in 1956, but was withdrawn from the market in 1999. On February 4, 2011, the FDA approved Makena, manufactured by KV Pharmaceuticals (formerly Gestiva), for the prevention of preterm birth in women with a history of preterm labor, sparking pricing controversy. In April 2023, the FDA revoked approval for Makena and its generic versions due to unfavorable risk-benefit assessments. Hydroxyprogesterone caproate is a synthetic progestin with a mechanism of action similar to endogenous progestins and can be used for hormone therapy or as a female contraceptive. Hydroxyprogesterone caproate mimics the effects of progesterone, binding to and activating nuclear progesterone receptors in the reproductive system. This causes the ligand-receptor complex to translocate to the cell nucleus, where it binds to target genes and promotes their expression. Due to the negative feedback mechanism of progesterone, this drug also inhibits the release of luteinizing hormone (LH) from the pituitary gland, thereby suppressing ovulation and altering cervical mucus and the endometrium. Furthermore, without stimulation of LH, the release of estrogen from the ovaries ceases, thus inhibiting the growth of estrogen-sensitive tumor cells. 17α-Hydroxyprogesterone caproate is a synthetic steroid hormone, similar to medroxyprogesterone acetate and megestrol acetate. It is an ester derivative of 17α-hydroxyprogesterone, derived from hexanoic acid (hexanoic acid). 17α-Hydroxyprogesterone caproate was marketed by Bristol-Myers Squibb under the brand name Delalutin and was approved by the U.S. Food and Drug Administration (FDA) in 1956, but was withdrawn from the market in 1999. Cytyc is seeking FDA approval to market 17α-hydroxyprogesterone caproate under the brand name Gestiva for the prevention of recurrent preterm birth in women with a history of preterm birth. [Wikipedia]
Hydroxyprogesterone derivatives are progestins used to reduce the risk of recurrent miscarriage and preterm birth. It is also used in combination with estrogen to treat menstrual disorders.
See also: Hydroxyprogesterone (containing the active ingredient).
Drug Indications

Hydroxyprogesterone caproate was previously approved in the United States for the prevention of recurrent spontaneous preterm birth in women with a history of spontaneous preterm birth in singleton pregnancies. This indication was withdrawn by the FDA in April 2023. Hydroxyprogesterone caproate remains approved in other jurisdictions for the treatment of primary and secondary amenorrhea, luteal insufficiency, and the prevention of preterm birth.
FDA Label
Mechanism of Action

The mechanism by which progesterone prevents preterm birth is not fully understood, but may involve multiple pathways. Progesterone plays a crucial role in regulating the female reproductive system and is essential for successful embryo implantation and maintaining pregnancy. It exerts its effects by binding to progesterone receptors in the uterus, ovaries, mammary glands, and central nervous system. These receptors exist in two subtypes, PR-A and PR-B. The binding of progesterone to these receptors ultimately leads to the regulation of gene transcription. This produces an anti-inflammatory effect, thereby reducing the pro-inflammatory state that occurs at the onset of labor and maintaining uterine rest by stabilizing progesterone's action on the myometrium.
Hydroxyprogesterone caproate is approved by the FDA for the prevention of preterm birth in women with a singleton pregnancy and a history of spontaneous preterm birth. It is administered as a weekly intramuscular injection starting in the second trimester. The compound was previously marketed as Delalutin and is available as a generic formulation. Research applications include studying progesterone receptor signaling, reproductive physiology, and pregnancy maintenance.

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.)