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.
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 is also used for the termination of pregnancy in the 2nd trimester.[3]
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[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 microgram/milliliter solution of the active drug. The drug must be refrigerated at a temperature between 2 – 8 degrees Celsius.[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.
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.
^
abcHemabate [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.
PMID4416671.
^G. L. Bundy et al., DE 2121980, Gordon, Leonard; Pike, John Edward & Schneider, William Paul, "Verfahren zur Herstellung nueur Prostansäurederivate [Process for the production of new prostanoic acid derivatives]", published 1971-11-25, assigned to
The Upjohn Co.
Further reading
Indman PD (February 2004). "Use of carboprost to facilitate hysteroscopic resection of submucous myomas". The Journal of the American Association of Gynecologic Laparoscopists. 11 (1): 68–72.
doi:
10.1016/S1074-3804(05)60014-X.
PMID15104835.
Vukelić J (2001). "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.
PMID11436877.
Ippoliti C, Przepiorka D, Mehra R, Neumann J, Wood J, Claxton D, et al. (December 1995). "Intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation". Urology. 46 (6): 811–5.
doi:
10.1016/S0090-4295(99)80349-5.
PMID7502421.