Chemistry:Carboprost

Short description: Chemical compound

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) 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
ChEBI	CHEBI:3403
ChEMBL	ChEMBL1237122 N
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 (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's main use is in the obstetrical emergency of postpartum hemorrhage which reduces postpartum bleeding during these circumstances.

Indication

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. Carboprost is also used for the termination of pregnancy in the 2nd trimester.

Contraindication

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

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 microgram/milliliter solution of the active drug. The drug must be refrigerated at a temperature between 2 – 8 degrees Celsius.

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:; 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.

Further reading

• "Use of carboprost to facilitate hysteroscopic resection of submucous myomas". The Journal of the American Association of Gynecologic Laparoscopists 11 (1): 68–72. February 2004. doi:10.1016/S1074-3804(05)60014-X. PMID 15104835. 
• "Second trimester pregnancy termination in primigravidas by double application of dinoprostone gel and intramuscular administration of carboprost tromethamine". Medicinski Pregled 54 (1–2): 11–6. 2001. PMID 11436877. 
• "Intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation". Urology 46 (6): 811–5. December 1995. doi:10.1016/S0090-4295(99)80349-5. PMID 7502421. 

External links

• Carboprost at the US National Library of Medicine Medical Subject Headings (MeSH)