Carboprost Tromethamine

Identification

Name
Carboprost Tromethamine
Accession Number
DB00429  (APRD00847)
Type
Small Molecule
Groups
Approved
Description

A nonsteroidal abortifacient agent that is effective in both the first and second trimesters of pregnancy. [PubChem]

Structure
Thumb
Synonyms
  • (15S)-15-Methyl-pgf2alpha tromethamine salt
  • (15S)-15-Methylprostaglandin F2alpha tromethamine
  • 1,3-Dihydroxy-2-(hydroxymethyl)propan-2-aminium (5Z,9alpha,11beta,13e,15S)-9,11,15-trihydroxy-15-methylprosta-5,13-dien-1-oate
  • 15(S)-15-Methyl-pgf2alpha tromethamine salt
  • 15(S)-15-Methylprostaglandin F2alpha tromethamine
  • Carboprost
  • Carboprost trometamol
  • Methyldinoprost
External IDs
U 32921 E
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
HemabateSolution250 mcgIntramuscularPfizer1997-11-28Not applicableCanada
HemabateInjection, solution250 ug/1mLIntramuscularPharmacia & Upjohn Inc1979-01-09Not applicableUs
International/Other Brands
Carboprost / Deviprost (Dr. Reddy's) / Prostin 15M (Pfizer) / Prostinfenem (Pfizer) / Prostodin (AstraZeneca)
Categories
UNII
U4526F86FJ
CAS number
58551-69-2
Weight
Average: 489.6426
Monoisotopic: 489.330167485
Chemical Formula
C25H47NO8
InChI Key
UMMADZJLZAPZAW-OVXHCKHTSA-N
InChI
InChI=1S/C21H36O5.C4H11NO3/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;5-4(1-6,2-7)3-8/h5,7,12,14,16-19,22-23,26H,3-4,6,8-11,13,15H2,1-2H3,(H,24,25);6-8H,1-3,5H2/b7-5-,14-12+;/t16-,17-,18+,19+,21+;/m1./s1
IUPAC Name
1,3-dihydroxy-2-(hydroxymethyl)propan-2-aminium (5Z)-7-[(1R,2R,3S,5S)-3,5-dihydroxy-2-[(1E,3S)-3-hydroxy-3-methyloct-1-en-1-yl]cyclopentyl]hept-5-enoate
SMILES
OCC([NH3+])(CO)CO.CCCCC[C@@](O)(C)\C=C\[C@H]1[C@@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(=O)[O-]

Pharmacology

Indication

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: 1. Failure of expulsion of the fetus during the course of treatment by another method; 2. Premature rupture of membranes in intrauterine methods with loss of drug and insufficient or absent uterine activity; 3. Requirement of a repeat intrauterine instillation of drug for expulsion of the fetus; 4. Inadvertent or spontaneous rupture of membranes in the presence of a previable fetus and absence of adequate activity for expulsion. Also for the treatment of postpartum hemorrhage due to uterine atony which has not responded to conventional methods of management.

Associated Conditions
Associated Therapies
Pharmacodynamics

Carboprost tromethamine administered intramuscularly stimulates in the gravid uterus myometrial contractions similar to labor contractions at the end of a full term pregnancy. Whether or not these contractions result from a direct effect of carboprost on the myome-trium has not been determined. Nonetheless, they evacuate the products of conception from the uterus in most cases. Postpartum, the resultant myometrial contractions provide hemostasis at the site of placentation. Carboprost tromethamine also stimulates the smooth muscle of the human gastrointestinal tract. This activity may produce the vomiting or diarrhea or both that is common when carbo-prost tromethamine is used to terminate pregnancy and for use postpartum. In laboratory animals and also in humans carboprost tromethamine can elevate body temperature. With the clinical doses of carboprost trometh-amine used for the termination of pregnancy, and for use postpartum, some patients do experience transient temperature increases. In laboratory animals and in humans large doses of carboprost tromethamine can raise blood pressure, probably by contracting the vascular smooth muscle. With the doses of carboprost tromethamine used for terminating pregnancy, this effect has not been clinically significant. In laboratory animals and also in humans carboprost tromethamine can elevate body temperature. With the clinical doses of carboprost tromethamine used for the termination of pregnancy, some patients do experience temperature increases. In some patients, carboprost tromethamine may cause transient bronchoconstriction.

Mechanism of action

Carboprost is a synthetic prostaglandin. It binds the prostaglandin E2 receptor, causing myometrial contractions, casuing the induction of labour or the expulsion of the placenta. Prostaglandins occur naturally in the body and act at several sites in the body including the womb (uterus). They act on the muscles of the womb, causing them to contract.

TargetActionsOrganism
AProstaglandin E2 receptor EP1 subtype
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Metabolized in the lungs and liver. Metabolites are excreted in urine.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Symptoms of overdose include irritation, nausea, vomiting, diarrhea, coughing, dyspnea, asthma, hypertension, flushing, and pyrexia.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
CarbetocinCarboprost Tromethamine may increase the uterotonic activities of Carbetocin.
DemoxytocinCarboprost Tromethamine may increase the uterotonic activities of Demoxytocin.
DinoprostCarboprost Tromethamine may increase the uterotonic activities of Dinoprost.
Dinoprost TromethamineCarboprost Tromethamine may increase the uterotonic activities of Dinoprost Tromethamine.
DinoprostoneCarboprost Tromethamine may increase the uterotonic activities of Dinoprostone.
ErgonovineCarboprost Tromethamine may increase the uterotonic activities of Ergonovine.
ErgotamineCarboprost Tromethamine may increase the uterotonic activities of Ergotamine.
GemeprostCarboprost Tromethamine may increase the uterotonic activities of Gemeprost.
MethylergometrineCarboprost Tromethamine may increase the uterotonic activities of Methylergometrine.
MisoprostolCarboprost Tromethamine may increase the uterotonic activities of Misoprostol.
Food Interactions
Not Available

References

Synthesis Reference

Ming Li, "CRYSTALS OF CARBOPROST TROMETHAMINE AND THE PREPARATION METHOD AS WELL AS THE USES THEREOF." U.S. Patent US20130190404, issued July 25, 2013.

US20130190404
General References
Not Available
External Links
Human Metabolome Database
HMDB0014573
KEGG Drug
D00682
PubChem Compound
45266502
PubChem Substance
46508118
ChemSpider
26333214
ChEBI
3404
ChEMBL
CHEMBL1237105
Therapeutic Targets Database
DAP001215
PharmGKB
PA164754883
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
ATC Codes
G02AD04 — Carboprost
AHFS Codes
  • 76:00.00 — Oxytocics
MSDS
Download (49.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentArterial Hypotension / Uterine Atony1
4Not Yet RecruitingTreatmentPostpartum Haemorrhage (PPH) / Uterine Atony1
Not AvailableCompletedTreatmentPostpartum Haemorrhage (PPH)2
Not AvailableRecruitingTreatmentPostpartum Haemorrhage (PPH)1

Pharmacoeconomics

Manufacturers
  • Pharmacia and upjohn co
  • Hospira inc
Packagers
  • Hospira Inc.
  • Pharmacia Inc.
Dosage forms
FormRouteStrength
Injection, solutionIntramuscular250 ug/1mL
SolutionIntramuscular250 mcg
Prices
Unit descriptionCostUnit
Hemabate 250 mcg/ml ampul92.89USD ml
Tham iv solution0.49USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)95-105 °CNot Available
water solubilityCarboprost tromethamine dissolves readily in water at room temperature at a concentration greater than 75 mg/mL.Not Available
logP3.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0622 mg/mLALOGPS
logP1.07ALOGPS
logP2.89ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)4.36ChemAxon
pKa (Strongest Basic)-1.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area100.82 Å2ChemAxon
Rotatable Bond Count15ChemAxon
Refractivity115.95 m3·mol-1ChemAxon
Polarizability42.51 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.5755
Blood Brain Barrier-0.5581
Caco-2 permeable-0.6594
P-glycoprotein substrateSubstrate0.6894
P-glycoprotein inhibitor INon-inhibitor0.9445
P-glycoprotein inhibitor IINon-inhibitor0.9643
Renal organic cation transporterNon-inhibitor0.8922
CYP450 2C9 substrateNon-substrate0.8241
CYP450 2D6 substrateNon-substrate0.7916
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.7693
CYP450 2C9 inhibitorNon-inhibitor0.8874
CYP450 2D6 inhibitorNon-inhibitor0.7649
CYP450 2C19 inhibitorNon-inhibitor0.8534
CYP450 3A4 inhibitorNon-inhibitor0.943
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.933
Ames testNon AMES toxic0.9008
CarcinogenicityNon-carcinogens0.9422
BiodegradationReady biodegradable0.5
Rat acute toxicity2.4308 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9511
hERG inhibition (predictor II)Non-inhibitor0.9008
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as prostaglandins and related compounds. These are unsaturated carboxylic acids consisting of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Fatty Acyls
Sub Class
Eicosanoids
Direct Parent
Prostaglandins and related compounds
Alternative Parents
Long-chain fatty acids / Branched fatty acids / Hydroxy fatty acids / Unsaturated fatty acids / Cyclopentanols / Tertiary alcohols / 1,2-aminoalcohols / Cyclic alcohols and derivatives / Carboxylic acids / Monocarboxylic acids and derivatives
show 8 more
Substituents
Prostaglandin skeleton / Long-chain fatty acid / Branched fatty acid / Hydroxy fatty acid / Fatty acid / Cyclopentanol / Unsaturated fatty acid / Cyclic alcohol / Tertiary alcohol / 1,2-aminoalcohol
show 20 more
Molecular Framework
Not Available
External Descriptors
organoammonium salt (CHEBI:3404)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Prostaglandin e receptor activity
Specific Function
Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(q) proteins which activate a phosphatidylinositol-calcium second messenger system. May play a role as an importa...
Gene Name
PTGER1
Uniprot ID
P34995
Uniprot Name
Prostaglandin E2 receptor EP1 subtype
Molecular Weight
41800.655 Da
References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  2. Hay A, Wood S, Olson D, Slater DM: Labour is associated with decreased expression of the PGF2alpha receptor (PTGFR) and a novel PTGFR splice variant in human myometrium but not decidua. Mol Hum Reprod. 2010 Oct;16(10):752-60. doi: 10.1093/molehr/gaq046. Epub 2010 Jun 2. [PubMed:20519365]
  3. Tsuboi K, Ichikawa A: [Reproduction physiology and prostanoids]. Nihon Yakurigaku Zasshi. 2001 Apr;117(4):267-73. [PubMed:11338376]
  4. Carrasco MP, Asboth G, Phaneuf S, Lopez Bernal A: Activation of the prostaglandin FP receptor in human granulosa cells. J Reprod Fertil. 1997 Nov;111(2):309-17. [PubMed:9462300]

Drug created on June 13, 2005 07:24 / Updated on November 21, 2018 07:14