Carboprost methylate
[CAS# 62776-96-9]

Identification

• Classification: API >> Hormone and endocrine-regulating drugs
• Name: Carboprost methylate
• Synonyms: PG 05; (5Z,9alpha,11alpha,13E,15S)-(±)-9,11,15-Trihydroxy-15-methyl-prosta-5,13-dien-1-oic acid methyl ester
• Molecular Formula: C₂₂H₃₈O₅
• Molecular Weight: 382.53
• CAS Registry Number: 62776-96-9
• SMILES: CCCCC[C@](C)(O)/C=C/[C@@H]1[C@@H](C/C=C\CCCC(=O)OC)[C@@H](O)C[C@H]1O

Properties

• Solubility: Practically insoluble (0.046 g/L) (25 ºC), Calc.^*
• Density: 1.096±0.06 g/cm³ (20 ºC 760 Torr), Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2013 ACD/Labs)

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P280-P305+P351+P338

Discovory and Applicatios

Carboprost tromethamine is a synthetic analogue of the naturally occurring prostaglandin F_2α (PGF_2α) in which a methyl group is introduced at the C‑15 position (15‑methyl‑PGF_2α), and the compound is formulated as the tromethamine (tris(hydroxymethyl)aminomethane) salt to enhance aqueous solubility and formulation stability. The molecular formula of the tromethamine salt is C₂₅H₄₇NO₈, with a molecular weight of approximately 489.65. The structural modification compared to PGF_2α confers increased resistance to enzymatic oxidation at the C‑15 hydroxyl, thereby prolonging the biological activity of the compound.

The discovery and development of carboprost tromethamine stemmed from efforts to create potent uterotonic prostaglandin analogues with enhanced pharmacokinetics and formulation suitability for obstetric use. The 15‑methyl substitution was found to impede the rapid metabolic inactivation seen with many native prostaglandins, enabling longer duration of action in the uterus. The tromethamine salt form was selected to produce a stable, injectable aqueous preparation suitable for intramuscular administration in obstetric emergencies such as postpartum hemorrhage and for therapeutic abortion in the second trimester.

Clinically, carboprost tromethamine is indicated for treatment of postpartum uterine atony with hemorrhage when standard therapies (such as oxytocin and uterine massage) have failed, and for second trimester pregnancy termination under appropriate conditions. The mechanism of action involves binding to prostanoid FP receptors in the myometrium, leading to increased intracellular calcium, sustained uterine contractions, and enhanced uterine tone. These contractions promote expulsion of uterine contents or hemostasis at the placental implantation site. Because of its potent uterotonic activity and formulation as an injectable solution, carboprost tromethamine must be administered in a hospital setting by experienced personnel and with readiness for acute interventions.

In terms of pharmacodynamics and kinetics, intramuscular administration leads to peak plasma concentrations within minutes and effective uterine contraction shortly thereafter. Adverse effects are consistent with prostaglandin activity on smooth muscle and include nausea, vomiting, diarrhea, flushing, transient elevated temperature, bronchospasm, and elevated blood pressure. Contraindications include active cardiac, pulmonary, renal, or hepatic disease, and use in cases where uterine stimulation is contraindicated. Because of its potency and risk profile, dosing is carefully regulated—typical dosing for postpartum hemorrhage is 250 µg intramuscularly, which may be repeated at specified intervals up to a maximum cumulative dose.

From a formulation and chemical perspective, carboprost tromethamine illustrates how medicinal chemistry of prostaglandin analogues can combine structural modifications (15‑methyl substitution) with salt formulation strategies to achieve clinically useful agents with improved stability, solubility, and duration of action. Its development underscores the importance of precise stereochemistry, side‑chain modification, and tailored formulation in converting bio‑active but metabolically labile compounds into therapeutically viable drugs.

References

Bai J, Sun Q, Zhai H (2014) A comparison of oxytocin and carboprost tromethamine in the prevention of postpartum hemorrhage in high‑risk patients undergoing cesarean delivery. Experimental and Therapeutic Medicine 7 46–50 DOI: 10.3892/etm.2013.1379