Carboprost

Carboprost (INN, trade names for the tromethamine salts Hemabate, Tham) is a synthetic prostaglandin analogue of PGF_2α (specifically, it is 15-methyl-PGF_2α) with oxytocic properties.

Carboprost

Clinical data
Trade names	Hemabate
AHFS/Drugs.com	Micromedex Detailed Consumer Information
MedlinePlus	a600042
Pregnancy category	AU: D
Routes of administration	Intramuscular
ATC code	G02AD04 (WHO)
Legal status
Legal status	AU: S4 (Prescription only)[1] In general: ℞ (Prescription only)
Identifiers
IUPAC name (5Z,9α,11α,13E,15S)-9,11,15-trihydroxy-15- methylprosta-5,13-dien-1-oic acid
CAS Number	35700-23-3 Y tromethamine : 58551-69-2 Y
PubChem CID	5281075
DrugBank	DB00429 N
ChemSpider	4444532 Y
UNII	7B5032XT6O  tromethamine : U4526F86FJ Y
KEGG	D02343
ChEBI	CHEBI:3403
ChEMBL	ChEMBL1237122 N
CompTox Dashboard (EPA)	DTXSID4022739
Chemical and physical data
Formula	C21H36O5
Molar mass	368.514 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C(O)CCC/C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1/C=C/[C@](O)(C)CCCCC
InChI InChI=1S/C21H36O5/c1-3-4-9-13-21(2,26)14-12-17-16(18(22)15-19(17)23)10-7-5-6-8-11-20(24)25/h5,7,12,14,16-19,22-23,26H,3-4,6,8-11,13,15H2,1-2H3,(H,24,25)/b7-5-,14-12+/t16-,17-,18+,19-,21+/m1/s1 Y Key:DLJKPYFALUEJCK-IIELGFQLSA-N Y
NY (what is this?)  (verify)

Carboprost's main use is to reduce postpartum bleeding during the obstetrical emergency of postpartum hemorrhage.

Indication

Carboprost is used in postpartum hemorrhage caused by uterine atony not controlled by other methods. One study has shown that carboprost tromethamine is more effective than oxytocin in preventing postpartum hemorrhage in high-risk patients undergoing cesarean delivery.^[2]

Carboprost was the first drug widely used for medication abortions. It is still sometimes used for second trimester abortions, but has generally been supplanted by the mifepristone/misoprostol combination.^{[3][4][5][6][7][8]}

Contraindication

Carboprost is contraindicated in severe cardiovascular, renal, and hepatic disease. It is also contraindicated in acute pelvic inflammatory disease. Hypersensitivity to carboprost or any of its components is also a contraindication.^[3]

Precautions

• asthma
• anemia
• jaundice
• diabetes mellitus
• seizure disorders
• past uterine surgery

Adverse effects

• diarrhea (most common, may be sudden in onset)
• flushing or hot flashes
• fever
• chills
• nausea/vomiting

Storage and availability

Carboprost is supplied with its salt derivative tromethamine in 1-milliliter ampules containing a 250 mcg/mL solution of the active drug. The drug must be kept refrigerated at 2–8 °C (36–46 °F).^[3]

Synthesis

A significant deactivating metabolic transformation of natural prostaglandins is enzymatic oxidation of the C-15 hydroxyl to the corresponding ketone. This is prevented, with retention of activity, by methylation to give the C-15 tertiary carbinol series.

Carboprost synthesis:;^[9][10][11] G. L. Bundy, U.S. patent 3,728,382 (1973 to Upjohn).

This molecular feature is readily introduced at the stage of the Corey lactone (1) by reaction with methyl Grignard reagent or trimethylaluminium. The resulting mixture of tertiary carbinols (2) is transformed to oxytocic carboprost (3) by standard transformations, including separation of diastereomers, so that the final product is the C-15 analogue. This diastereomer is reputably freeer of prostaglandin side effects than the C-15 (S) isomer.