Carboprost

Carboprost
Systematic (IUPAC) name
(5Z,9α,11α,13E,15S)-9,11,15-trihydroxy-15- methylprosta-5,13-dien-1-oic acid
Clinical data
AHFS/Drugs.com Micromedex Detailed Consumer Information
MedlinePlus a600042
Pregnancy
category
  • c
Routes of
administration		 Intramuscular
Legal status
Legal status
  • ℞ (Prescription only)
Identifiers
CAS Number 58551-69-2 YesY
ATC code G02AD04 (WHO)
PubChem CID 5281075
DrugBank DB00429 N
ChemSpider 4444532 YesY
UNII U4526F86FJ YesY
ChEMBL CHEMBL1237122 N
Chemical data
Formula C21H36O5
Molar mass 368.508 g/mol
 NYesY (what is this?)  (verify)

Carboprost (INN, trade names for the tromethamine salts Hemabate, Tham) is a synthetic prostaglandin analogue of PGF2α (specifically, it is 15-methyl-PGF2α) with oxytocic properties.

Carboprost induces contractions and can trigger abortion in early pregnancy. It also reduces postpartum bleeding.

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 caesarian delivery.[1] Carboprost is also used for the termination of pregnancy in the 2nd trimester.[2]

Unlabeled use:

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

Adverse Effects

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 sepoaration 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.

See also

References

  1. ↑ 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.". Journal of Experimental and Therapeutic Medicine 7 (1): 46–50. doi:10.3892/etm.2013.1379. PMID 24348762.
  2. 1 2 3 Hemabate [Package Insert]. New York, NY: Pharmacia and Upjohn Company; 2014.
  3. ↑ Yankee, Ernest W.; Axen, Udo; Bundy, Gordon L. (1974). "Total synthesis of 15-methylprostaglandins". Journal of the American Chemical Society 96 (18): 5865. doi:10.1021/ja00825a027. PMID 4416671.
  4. ↑ Ann. N.Y. Acad. Sci. 180, 76 (1971).

External links


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