CARBOPROST

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H36O5
Molecular Weight	368.5075
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCC[C@](C)(O)\C=C\[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O

InChI

InChIKey=DLJKPYFALUEJCK-IIELGFQLSA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/017989s019lbl.pdf
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/monograph/carboprost-tromethamine.html

Carboprost is an analogue of naturally occurring prostaglandin F2alpha. Administered intramuscularly carboprost stimulates in the gravid uterus myometrial contractions similar to labor contractions at the end of a full term pregnancy. It is indicated for aborting pregnancy between the 13th and 20th weeks of gestation as calculated from the first day of the last normal menstrual period and for the treatment of postpartum hemorrhage due to uterine atony, which has not responded to conventional methods of management. The most frequent adverse reactions observed are related to its contractile effect on smooth muscle: vomiting, diarrhea, nausea, fever and flushing. Carboprost may augment the activity of other oxytocic agents. Concomitant use with other oxytocic agents is not recommended.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Prostanoid FP receptor 21 Target ID: CHEMBL1987 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/5281074	Agonist 2678
Prostanoid EP1 receptor 14 Target ID: CHEMBL1811 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/5281074 \| https://www.drugbank.ca/drugs/DB00429	Agonist 2678
menstrual cycle 3 Target ID: GO:0044850 Sources: https://www.ncbi.nlm.nih.gov/pubmed/531221 \| https://www.ncbi.nlm.nih.gov/pubmed/6489542	Activator 1430
female pregnancy 3 Target ID: GO:0007565 Sources: https://www.ncbi.nlm.nih.gov/pubmed/531221 \| https://www.ncbi.nlm.nih.gov/pubmed/6489542	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Postpartum hemorrhage due to uterine atony 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/017989s019lbl.pdf	Primary		Approved 8429	HEMABATE Approved Use HEMABATE Sterile Solution is indicated for aborting pregnancy between the 13th and 20th weeks of gestation as calculated from the first day of the last normal menstrual period and in the following conditions related to second trimester abortion: Failure of expulsion of the fetus during the course of treatment by another method; Premature rupture of membranes in intrauterine methods with loss of drug and insufficient or absent uterine activity; Requirement of a repeat intrauterine instillation of drug for expulsion of the fetus; Inadvertent or spontaneous rupture of membranes in the presence of a previable fetus and absence of adequate activity for expulsion. HEMABATE is indicated for the treatment of postpartum hemorrhage due to uterine atony which has not responded to conventional methods of management. Prior treatment should include the use of intravenously administered oxytocin, manipulative techniques such as uterine massage and, unless contraindicated, intramuscular ergot preparations. Studies have shown that in such cases, the use of HEMABATE has resulted in satisfactory control of hemorrhage, although it is unclear whether or not ongoing or delayed effects of previously administered ecbolic agents have contributed to the outcome. In a high proportion of cases, HEMABATE used in this manner has resulted in the cessation of life threatening bleeding and the avoidance of emergency surgical intervention. Launch Date 1979
Aborting pregnancy 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/017989s019lbl.pdf	Preventing		Approved 8429	HEMABATE Approved Use HEMABATE Sterile Solution is indicated for aborting pregnancy between the 13th and 20th weeks of gestation as calculated from the first day of the last normal menstrual period and in the following conditions related to second trimester abortion: Failure of expulsion of the fetus during the course of treatment by another method; Premature rupture of membranes in intrauterine methods with loss of drug and insufficient or absent uterine activity; Requirement of a repeat intrauterine instillation of drug for expulsion of the fetus; Inadvertent or spontaneous rupture of membranes in the presence of a previable fetus and absence of adequate activity for expulsion. HEMABATE is indicated for the treatment of postpartum hemorrhage due to uterine atony which has not responded to conventional methods of management. Prior treatment should include the use of intravenously administered oxytocin, manipulative techniques such as uterine massage and, unless contraindicated, intramuscular ergot preparations. Studies have shown that in such cases, the use of HEMABATE has resulted in satisfactory control of hemorrhage, although it is unclear whether or not ongoing or delayed effects of previously administered ecbolic agents have contributed to the outcome. In a high proportion of cases, HEMABATE used in this manner has resulted in the cessation of life threatening bleeding and the avoidance of emergency surgical intervention. Launch Date 1979

C_max

Value	Dose	Co-administered	Analyte	Population
2060 pg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/017989s019lbl.pdf	250 μg 1 times / 2 hours multiple, intramuscular dose: 250 μg route of administration: Intramuscular experiment type: MULTIPLE co-administered:		CARBOPROST plasma	Homo sapiens population: PREGNANT age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1332 pg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/017989s019lbl.pdf	250 μg 1 times / 2 hours multiple, intramuscular dose: 250 μg route of administration: Intramuscular experiment type: MULTIPLE co-administered:		CARBOPROST plasma	Homo sapiens population: PREGNANT age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
20 min DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/017989s019lbl.pdf	250 μg 1 times / 2 hours multiple, intramuscular dose: 250 μg route of administration: Intramuscular experiment type: MULTIPLE co-administered:		CARBOPROST plasma	Homo sapiens population: PREGNANT age: ADULT sex: FEMALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3403	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3403
ZINC	ZINC000027641461	http://zinc15.docking.org/substances/ZINC000027641461

PubMed

Title	Date	PubMed
The mechanism of prostaglandin action on the pregnant human uterus.	1979 Feb	441437
The mechanism of prostaglandin action on the early pregnant human uterus.	1979 Sep	531221
Transport of prostaglandins through silicone rubber.	1981 May	7241365
Menses induction in rhesus monkeys using a controlled-release vaginal delivery system containing (15S) 15-methyl prostaglandin F2 alpha methyl ester.	1984 Oct	6489542
Drug release testing of a prostaglandin containing controlled-release vaginal device: development of a semi-automated method.	1985 Oct	4078708
The contributions of adrenal hormones, hemodynamic factors, and the endotoxin-related stress reaction to stable prostaglandin analog-induced peripheral lymphopenia and neutrophilia.	1988 Jan	3275734
Treatment of cyclophosphamide-induced hemorrhagic cystitis with prostaglandins.	1994 May	8068996
Uterotonic Medications: Oxytocin, Methylergonovine, Carboprost, Misoprostol.	2017 Jun	28526143

Patents

Sample Use Guides

In Vivo Use Guide

1. Abortion and Indications 1–4: An initial dose of 1 mL of HEMABATE Sterile Solution (containing the equivalent of 250 micrograms of carboprost) is to be administered deep in the muscle with a tuberculin syringe. Subsequent doses of 250 micrograms should be administered at 1½ to 3½ hour intervals depending on uterine response. An optional test dose of 100 micrograms (0.4 mL) may be administered initially. The dose may be increased to 500 micrograms (2 mL) if uterine contractility is judged to be inadequate after several doses of 250 micrograms (1 mL). The total dose administered of carboprost tromethamine should not exceed 12 milligrams and continuous administration of the drug for more than two days is not recommended. 2. For Refractory Postpartum Uterine Bleeding: An initial dose of 250 micrograms of HEMABATE Sterile Solution (1 mL of HEMABATE) is to be given deep, intramuscularly. In clinical trials it was found that the majority of successful cases (73%) responded to single injections. In some selected cases, however, multiple dosing at intervals of 15 to 90 minutes was carried out with successful outcome. The need for additional injections and the interval at which these should be given can be determined only by the attending physicians as dictated by the course of clinical events. The total dose of HEMABATE should not exceed 2 milligrams (8 doses).

Route of Administration: Intramuscular

In Vitro Use Guide

The pEC50 values obtained for carboprost (as a measure of potency) on 146 myometrial strips from 19 donors, in relation to the two contractile parameters (the maximum amplitude (MAMP) and the mean contractile force above baseline (MCF)) were 6.0 for MAMP and 5.8 for MCF.

Name

Type

Language

CARBOPROST

Official Name

English

15-METHYL-PGF2.ALPHA.

Common Name

English

CARBOPROST [USAN]

Common Name

English

carboprost [INN]

Common Name

English

CARBOPROST [MART.]

Common Name

English

(E,Z)-(1R,2R,3R,5S)-7-[3,5-Dihydroxy-2-[(3S)-(3-hydroxy-3-methyl-1-octenyl)]cyclopentyl]-5-heptenoic acid

Systematic Name

English

15-METHYLPROSTAGLANDIN F2.ALPHA.

Common Name

English

(15S)-15-METHYLPROSTAGLANDIN F(SUB 2.ALPHA.)

Common Name

English

PROSTA-5,13-DIEN-1-OIC ACID, 9,11,15-TRIHYDROXY-15-METHYL-, (5Z,9.ALPHA.,11.ALPHA.,13E,15S)-

Common Name

English

CARBOPROST [MI]

Common Name

English

U-32921

Code

English

U-32,921

Code

English

CARBOPROST [VANDF]

Common Name

English

(5Z,9.ALPHA.,11.ALPHA.,13E,15S)-9,11,15-TRIHYDROXY-15-METHYLPROSTA-5,13-DIEN-1-OIC ACID

Systematic Name

English

(15S)-15-METHYLPROSTAGLANDIN F2.ALPHA.

Common Name

English

15-METHYLPROSTAGLANDIN F2BETA, (15S)-

Common Name

English

(15S)-15-METHYL-PGF2.ALPHA.

Common Name

English

Carboprost [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-ATC

G02AD04