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Revision as of 20:11, 10 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank', 'ChEMBL').← Previous edit Latest revision as of 16:59, 17 September 2024 edit undoNoleander (talk | contribs)Autopatrolled, Extended confirmed users, Pending changes reviewers, Rollbackers32,385 edits →Indication: abortion: add more cites; clarify that it is no longer commonly used for that purpose. 
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{{Short description|Chemical compound}}
{{Drugbox
{{Infobox drug
| Verifiedfields = changed | Verifiedfields = changed
| verifiedrevid = 408786343 | verifiedrevid = 460018936
| IUPAC_name = (5''Z'',9α,11α,13''E'',15''S'')-9,11,15-trihydroxy-15- methylprosta-5,13-dien-1-oic acid | IUPAC_name = (5''Z'',9α,11α,13''E'',15''S'')-9,11,15-trihydroxy-15- methylprosta-5,13-dien-1-oic acid
| image = Carboprost.svg | image = Carboprost.svg


<!--Clinical data--> <!--Clinical data-->
| tradename = | pronounce =
| tradename = Hemabate
| Drugs.com = {{drugs.com|CONS|carboprost}} | Drugs.com = {{drugs.com|CONS|carboprost}}
| MedlinePlus = a600042 | MedlinePlus = a600042
| licence_CA = <!-- Health Canada may use generic or brand name (generic name preferred) -->
| pregnancy_category = c
| licence_EU = <!-- EMA uses INN (or special INN_EMA) -->
| DailyMedID = <!-- DailyMed may use generic or brand name (generic name preferred) -->
| licence_US = <!-- FDA may use generic or brand name (generic name preferred) -->
| pregnancy_AU = D
| pregnancy_AU_comment =
| pregnancy_category =
| routes_of_administration = ]
| class =
| ATCvet =
| ATC_prefix = G02
| ATC_suffix = AD04
| ATC_supplemental =

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = <ref>{{cite web | title=Carboprost-REACH (Reach Pharmaceuticals Pty Ltd) | website=Therapeutic Goods Administration (TGA) | date=28 July 2023 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/carboprost-reach-reach-pharmaceuticals-pty-ltd | access-date=10 September 2023}}</ref>
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment =
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_US_comment =
| legal_EU =
| legal_EU_comment =
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = Rx-only | legal_status = Rx-only
| routes_of_administration = Intravenous


<!--Pharmacokinetic data--> <!--Pharmacokinetic data-->
| bioavailability = | bioavailability =
| protein_bound = | protein_bound =
| metabolism = | metabolism =
| elimination_half-life = | elimination_half-life =


<!--Identifiers--> <!--Identifiers-->
| index2_label = tromethamine 
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}} | CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 58551-69-2 | CAS_number = 35700-23-3
| CAS_number2_Ref = {{cascite|correct|CAS}}
| ATC_prefix = G02
| CAS_number2 = 58551-69-2
| ATC_suffix = AD04
| UNII_Ref = {{fdacite|correct|FDA}}
| ATC_supplemental =
| UNII = 7B5032XT6O 
| UNII2_Ref = {{fdacite|correct|FDA}}
| UNII2 = U4526F86FJ
| PubChem = 5281075 | PubChem = 5281075
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = <!-- blanked - oldvalue: APRD00847 --> | DrugBank = DB00429
| ChEBI = 3403
| KEGG = D02343
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4444532 | ChemSpiderID = 4444532
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = U4526F86FJ
| ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = <!-- blanked - oldvalue: 1201299 --> | ChEMBL = 1237122
<!--Chemical data-->
| C=21 | H=36 | O=5
| C=21 | H=36 | O=5
| molecular_weight = 368.508 g/mol
| smiles = O=C(O)CCC/C=C/C1(O)C(O)1/C=C/(O)(C)CCCCC | smiles = O=C(O)CCC/C=C/C1(O)C(O)1/C=C/(O)(C)CCCCC
| InChI = 1/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
| InChIKey = DLJKPYFALUEJCK-MRVZPHNRBG
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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 | StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = DLJKPYFALUEJCK-IIELGFQLSA-N | StdInChIKey = DLJKPYFALUEJCK-IIELGFQLSA-N
|drug_name=|alt=|caption=|type=|pregnancy_US=}}
}}


'''Carboprost''' (], trade names for the ] salts '''Hemabate''', '''Tham''') is a synthetic ] analogue of PGF<sub>2α</sub> (specifically, it is 15-methyl-PGF<sub>2α</sub>) with ] properties. '''Carboprost''' (], trade names for the ] salts '''Hemabate''', '''Tham''') is a synthetic ] analogue of ] (specifically, it is 15-methyl-PGF<sub>2α</sub>) with ] properties.


Carboprost induces ] and can trigger abortion in early pregnancy. It also reduces ]. Carboprost's main use is in the obstetrical emergency of ] which reduces ] during these circumstances.


==Indication== == 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.<ref>{{cite journal | vauthors = Bai J, Sun Q, Zhai H | title = A comparison of oxytocin and carboprost tromethamine in the prevention of postpartum hemorrhage in high-risk patients undergoing cesarean delivery | journal = Experimental and Therapeutic Medicine | volume = 7 | issue = 1 | pages = 46–50 | date = January 2014 | pmid = 24348762 | pmc = 3861477 | doi = 10.3892/etm.2013.1379 }}</ref>
Used in postpartum hemorrhage caused by uterine atony not controlled by other methods.<br />Unlabeled use:
* Hemorrhagic Cystitis
* PID


Carboprost was the first drug widely used for ]s. It is still sometimes used for second trimester abortions, but has generally been supplanted by the ]/] combination.<ref name = HemabatePI>Hemabate . New York, NY: Pharmacia and Upjohn Company; 2014.</ref><ref name="Mayo">"Carboprost" - Drug fact sheet, Mayo Clinic. Last updated: July 01, 2024
==Contraindication==
https://www.mayoclinic.org/drugs-supplements/carboprost-intramuscular-route/proper-use/drg-20067975</ref><ref name="Vuk">Vukelić J. Second trimester pregnancy termination in primigravidas by double application of dinoprostone gel and intramuscular administration of carboprost tromethamine. Med Pregl. 2001 Jan-Feb;54(1-2):11-6. English, Croatian. PMID: 11436877.</ref><ref name="Byg">Bygdeman, M., & Gemzell-Danielsson, K. (2008). An Historical Overview of Second Trimester Abortion Methods. Reproductive Health Matters, 16(sup31), 196–204. https://doi.org/10.1016/S0968-8080(08)31385-8</ref><ref name="Sch">Schwallie PC, Lamborn KR. Induction of abortion by intramuscular administration of (15S)-15-methyl PGF2 alpha. An overview of 815 cases. J Reprod Med. 1979 Dec;23(6):289-93. PMID: 392084.</ref><ref name="Bha">Bhaskar A, Dimov V, Baliga S, Kinra G, Hingorani V, Laumas KR. Plasma levels of 15 (S) 15-methyl-PGF 2 alpha-methyl ester following vaginal administration for induction of abortion in women. ''Contraception''. 1979 Nov;20(5):519-31. doi: 10.1016/0010-7824(79)90057-x. PMID: 527343.</ref>
Contraindicated in severe cardiovascular, renal, and hepatic disease, also contraindicated in Pelvic Inflammatory Disease. Exert caution in asthmatic patients.


== Contraindication ==
==Precautions==
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<ref name = HemabatePI />

== Precautions ==
* asthma * asthma
* anemia * anemia
Line 66: Line 101:
* past uterine surgery * past uterine surgery


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


== Storage and Availability ==
==References==
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.<ref name = HemabatePI />

== 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.
|assign=]|inventor1-last=Gordon|inventor1-first=Leonard|inventor2-last=Pike|inventor2-first=John Edward|inventor3-last=Schneider|inventor3-first=William Paul}}</ref> G. L. Bundy, {{US patent|3728382}} (1973 to ]).]]
This molecular feature is readily introduced at the stage of the Corey lactone ('''1''') by reaction with methyl ] or ]. 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.

== References ==
{{reflist}} {{reflist}}


== Further reading ==
==External links==
{{refbegin}}
* {{cite journal | vauthors = Indman PD | title = Use of carboprost to facilitate hysteroscopic resection of submucous myomas | journal = The Journal of the American Association of Gynecologic Laparoscopists | volume = 11 | issue = 1 | pages = 68–72 | date = February 2004 | pmid = 15104835 | doi = 10.1016/S1074-3804(05)60014-X }}
* {{cite journal | vauthors = Vukelić J | title = Second trimester pregnancy termination in primigravidas by double application of dinoprostone gel and intramuscular administration of carboprost tromethamine | journal = Medicinski Pregled | volume = 54 | issue = 1–2 | pages = 11–6 | year = 2001 | pmid = 11436877 }}
* {{cite journal | vauthors = Ippoliti C, Przepiorka D, Mehra R, Neumann J, Wood J, Claxton D, Gajewski J, Khouri I, van Besien K, Andersson B | display-authors = 6 | title = Intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation | journal = Urology | volume = 46 | issue = 6 | pages = 811–5 | date = December 1995 | pmid = 7502421 | doi = 10.1016/S0090-4295(99)80349-5 }}
{{refend}}

== External links ==
* {{MeshName|Carboprost}} * {{MeshName|Carboprost}}
* {{cite journal | author = Indman P | title = Use of carboprost to facilitate hysteroscopic resection of submucous myomas. | journal = J Am Assoc Gynecol Laparosc | volume = 11 | issue = 1 | pages = 68–72 | year = 2004 | pmid = 15104835 | doi = 10.1016/S1074-3804(05)60014-X}}
* {{cite journal | author = Vukelić J | title = Second trimester pregnancy termination in primigravidas by double application of dinoprostone gel and intramuscular administration of carboprost tromethamine. | journal = Med Pregl | volume = 54 | issue = 1–2 | pages = 11–6 | year = 2001| pmid = 11436877}}
* {{cite journal | author = Ippoliti C, Przepiorka D, Mehra R, Neumann J, Wood J, Claxton D, Gajewski J, Khouri I, van Besien K, Andersson B | title = Intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation | journal = Urology | volume = 46 | issue = 6 | pages = 811–5 | year = 1995 | pmid = 7502421 | doi = 10.1016/S0090-4295(99)80349-5}}


{{Prostaglandins}} {{Prostaglandins}}
{{Oxytocics}} {{Oxytocics}}
{{Obstetric drugs}}
{{Prostanoidergics}}

] ]
]
] ]
]


{{genito-urinary-drug-stub}}

Latest revision as of 16:59, 17 September 2024

Chemical compound Pharmaceutical compound
Carboprost
Clinical data
Trade namesHemabate
AHFS/Drugs.comMicromedex Detailed Consumer Information
MedlinePlusa600042
Pregnancy
category
  • AU: D
Routes of
administration		Intramuscular
ATC code
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
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H36O5
Molar mass368.514 g·mol
3D model (JSmol)
SMILES
  • O=C(O)CCC/C=C/C1(O)C(O)1/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
  (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'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 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.

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.

References

  1. "Carboprost-REACH (Reach Pharmaceuticals Pty Ltd)". Therapeutic Goods Administration (TGA). 28 July 2023. Retrieved 10 September 2023.
  2. 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.
  3. ^ Hemabate . New York, NY: Pharmacia and Upjohn Company; 2014.
  4. "Carboprost" - Drug fact sheet, Mayo Clinic. Last updated: July 01, 2024 https://www.mayoclinic.org/drugs-supplements/carboprost-intramuscular-route/proper-use/drg-20067975
  5. Vukelić J. Second trimester pregnancy termination in primigravidas by double application of dinoprostone gel and intramuscular administration of carboprost tromethamine. Med Pregl. 2001 Jan-Feb;54(1-2):11-6. English, Croatian. PMID: 11436877.
  6. Bygdeman, M., & Gemzell-Danielsson, K. (2008). An Historical Overview of Second Trimester Abortion Methods. Reproductive Health Matters, 16(sup31), 196–204. https://doi.org/10.1016/S0968-8080(08)31385-8
  7. Schwallie PC, Lamborn KR. Induction of abortion by intramuscular administration of (15S)-15-methyl PGF2 alpha. An overview of 815 cases. J Reprod Med. 1979 Dec;23(6):289-93. PMID: 392084.
  8. Bhaskar A, Dimov V, Baliga S, Kinra G, Hingorani V, Laumas KR. Plasma levels of 15 (S) 15-methyl-PGF 2 alpha-methyl ester following vaginal administration for induction of abortion in women. Contraception. 1979 Nov;20(5):519-31. doi: 10.1016/0010-7824(79)90057-x. PMID: 527343.
  9. 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.
  10. 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. S2CID 34735617.
  11. G. L. Bundy et al., DE 2121980, Gordon, Leonard; Pike, John Edward & Schneider, William Paul, "Verfahren zur Herstellung nueur Prostansäurederivate ", 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. PMID 15104835.
  • 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. PMID 11436877.
  • 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. PMID 7502421.

External links

Eicosanoids
Precursor
Prostanoids
Prostaglandins (PG)
Precursor
Active
D/J
E/F
I
Thromboxanes (TX)
Leukotrienes (LT)
Precursor
Initial
SRS-A
Eoxins (EX)
Precursor
Eoxins
Nonclassic
By function
Uterotonics/labor inducers/oxytocics (G02A)
Cervical ripening
Ergot alkaloids
Prostaglandins and
analogues
Contraction induction
Obstetric drugs
Induction and augmentation of labour
Prevention and treatment of hemorrhage
Induction of abortion
Prostanoid signaling modulators
Receptor
(ligands)
DP (D2)Tooltip Prostaglandin D2 receptor
DP1Tooltip Prostaglandin D2 receptor 1
DP2Tooltip Prostaglandin D2 receptor 2
EP (E2)Tooltip Prostaglandin E2 receptor
EP1Tooltip Prostaglandin EP1 receptor
EP2Tooltip Prostaglandin EP2 receptor
EP3Tooltip Prostaglandin EP3 receptor
EP4Tooltip Prostaglandin EP4 receptor
Unsorted
FP (F2α)Tooltip Prostaglandin F receptor
IP (I2)Tooltip Prostacyclin receptor
TP (TXA2)Tooltip Thromboxane receptor
Unsorted
Enzyme
(inhibitors)
COX
(PTGS)
PGD2STooltip Prostaglandin D synthase
PGESTooltip Prostaglandin E synthaseHQL-79
PGFSTooltip Prostaglandin F synthaseBimatoprost
PGI2STooltip Prostacyclin synthaseTranylcypromine
TXASTooltip Thromboxane A synthase
Others
See also
Receptor/signaling modulators
Leukotriene signaling modulators
Categories: