Carboprost

Carboprost
Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
MedlinePlus	a600042
Pregnancy; category	c;
Routes of; administration	Intramuscular
ATC code	G02AD04 (WHO) ;
Legal status
Legal status	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 ;
PubChem CID	5281075;
DrugBank	DB00429 ;
ChemSpider	4444532 ;
UNII	U4526F86FJ;
ChEMBL	ChEMBL1237122 ;
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 ; Key:DLJKPYFALUEJCK-IIELGFQLSA-N ;
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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 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.[1] Carboprost is also used for the termination of pregnancy in the 2nd trimester.[2]

Unlabeled use:

Hemorrhagic Cystitis
PID

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[2] Exert caution in asthmatic patients as carboprost may cause bronchospasm.

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.[2]

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:[3][4] G. L. Bundy et al., DE 2121980; G. L. Bundy, U.S. Patent 3,728,382 (1971, 1973 both 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 porstaglandin side effects than the C-15 (S) isomer.

gollark: Happily, this also avoids issues with ordering effects.

gollark: Oh, obviously you would use a GTech™ nondestructive neural scanning array and spin up an instance of yourself to evaluate each.

gollark: Do you not have arbitrarily fast computers?

gollark: Why would you need *that*?

gollark: Your #3 entry was very cool. Highly palaiologistic-looking.

References

Bai J, Sun Q, Zhai H (January 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 (1): 46–50. doi:10.3892/etm.2013.1379. PMC 3861477. PMID 24348762.
Hemabate [Package Insert]. New York, NY: Pharmacia and Upjohn Company; 2014.
Yankee EW, Axen U, Bundy GL (September 1974). "Total synthesis of 15-methylprostaglandins". Journal of the American Chemical Society. 96 (18): 5865–76. doi:10.1021/ja00825a027. PMID 4416671.
Bundy G, Lincoln F, Nelson N, Pike J, Schneider W (April 1971). "Novel prostaglandin syntheses". Annals of the New York Academy of Sciences. 180 (1): 76–90. Bibcode:1971NYASA.180...76B. doi:10.1111/j.1749-6632.1971.tb53186.x. PMID 5286110.

External links

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

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[1] Bai J, Sun Q, Zhai H (January 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 (1): 46–50. doi:10.3892/etm.2013.1379. PMC 3861477. PMID 24348762.

[HemabatePI-2] Hemabate [Package Insert]. New York, NY: Pharmacia and Upjohn Company; 2014.

[3] Yankee EW, Axen U, Bundy GL (September 1974). "Total synthesis of 15-methylprostaglandins". Journal of the American Chemical Society. 96 (18): 5865–76. doi:10.1021/ja00825a027. PMID 4416671.

[4] Bundy G, Lincoln F, Nelson N, Pike J, Schneider W (April 1971). "Novel prostaglandin syntheses". Annals of the New York Academy of Sciences. 180 (1): 76–90. Bibcode:1971NYASA.180...76B. doi:10.1111/j.1749-6632.1971.tb53186.x. PMID 5286110.