NAV

Colfosceril palmitate

Identification

Summary

Colfosceril palmitate is a pulmonary surfactant used for the treatment of Respiratory Distress Syndrome (RDS) in premature infants.

Generic Name
Colfosceril palmitate
DrugBank Accession Number
DB09114
Background

Colfosceril palmitate is a synthetic pulmonary surfactant administered in infants with respiratory distress syndrome.1 It was part of the first generation of commercially available artificial surfactants.4 It was developed by Burroughs Wellcome and it was FDA approved on August 6, 1990.8 Nowadays colfosceril palmitate is under the state of canceled post-marketing.

Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Structure
Similar Structures
Weight
Average: 734.0389
Monoisotopic: 733.562155053
Chemical Formula
C40H80NO8P
Synonyms
  • Colfosceril palmitate
  • Colfoscerili palmitas
  • Dipalmitoylphosphatidylcholine
  • Palmitate de colfosceril
  • Palmitato de colfoscerilo
External IDs
  • 129Y83
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Pharmacology

Indication

Colfosceril palmitate is indicated for the treatment of respiratory distress syndrome (RDS) in premature infants. The official label is referred as a intratracheal suspension for prophylactic treatment of infants of less than 1350 grams of birth weight under risk of developing RDS, or in infants with birth weight greater than 1350 grams with pulmonary immaturity, or as rescue treatment of infants that already developed RDS.8 The central feature of RDS is a surfactant deficiency due to lung immaturity. This lung condition is more frequently presented due to risk factors like prematurity, delayed lung maturation caused by maternal diabetes or male gender, or surfactant dysfuntion due to perinatal asphyxia, pulmonary infection or delivery without labor.4

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Colfosceril palmitate has shown to significantly reduce the risk of pneumothoraces, pulmonary interstitial emphysema and mortality. Unlike naturals surfactants, colfosceril palmitate reduces the risk of bronchopulmonary dysplasia, intraventricular hemorrhage and patent ductus arteriosus.5 In clinical placebo-controlled trials, there was a significant reduction in the number of deaths attributed to hyaline membrane disease, the incidence of pulmonary air leaks, oxygen requirements and mean airway pressure.6 Some reports have indicated a lack of therapeutic effect due to the absence of surfactant protein.7

Mechanism of action

Treatment with colfosceril palmitate aims to reinflate a collapsed area of the lung, improve compliance and reduce intrapulmonary shunting.7 The actions of colfosceril palmitate are perfomed by replacing the defficient or innefective endogenous lung surfactant and thus, reducing the tension and stabilizing the alveoli from collapsing.9 Colfosceril palmitate will form a very thin film that will cover the surface of the alveolar cells and therefore it will reduce surface tension.10

Absorption

The absorption is done directly in the alveolus into the lung tissue.9 As the lung surfactant is distributed in the bronchi, bronchioles and alveoli, its highest concentration is at the alveolar air-fluid interface where it remains as a monolayer.2

Volume of distribution

Colfosceril palmitate is distributed uniformly to all lobes of the lung, distal airways and alveolar spaces.11 It will not enter the systemic circulation in healthy lungs, however when the integrity of the tissue is distrupted colfosceril can reach systemic circulation.2 Even 5 days after administration, there are traces of colfosceril palmitate retained in the body that represented 72% of the administered dose which by then have entered pathways of lipid metabolism to become tissue associated.3

Protein binding

Colfosceril palmitate stays and gets metabolized in the pulmunar tissue, thus it is not able to bind to plasma proteins.

Metabolism

Colfosceril palmitate is catabolized and reutilized for further synthesis and secretion in lung tissues.9

Route of elimination

After 5 days, most of the administered dose (56%) is distributed throughout the body with renal and fecal excretion being the minor elimination pathway representing the 4 and 2% of the eliminated dose respectively. The major route of elimination is by expelled air which accounts for 28% of the administered dose.3

Half-life

The half-life of colfosceril palmitate is registered to be in the range of 20-36 hours.11

Clearance

After 5 days of drug administration, the lung and liver would contain 10% of the administered dose and the elimination via renal excretion accounts only for 8% of the administered dose. This proved a very small renal clearance and confirmed that the major elimination route is by expired air.3

Adverse Effects
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Toxicity

In clinical trials, there are reports of pulmonary hemorrhage when colfosceril palmitate is administered in infants with a weight of fewer than 700 grams at birth. Another potential risk of the use of colfosceril palmitate is the formation of mucus plugging in the endotracheal tube which can be prevented by performing suction prior to dosing.8

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Exosurf NeonatalPowder, for suspension108 mg / vialEndotrachealGlaxosmithkline Inc1991-12-312003-01-17Canada flag
Exosurf NeonatalKit; Powder, for suspension108 mg / vialEndotrachealGlaxosmithkline Inc1991-12-312003-01-17Canada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
SurfaxinColfosceril palmitate (22.50 mg/1mL) + 1-palmitoyl-2-oleoyl-sn-glycero-3-(phospho-rac-(1-glycerol)), sodium salt (7.50 mg/1mL) + Palmitic Acid (4.05 mg/1mL) + Sinapultide (0.862 mg/1mL)SuspensionEndotrachealDiscovery Health2013-11-012016-01-19US flag

Categories

ATC Codes
R07AA01 — Colfosceril palmitate
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phosphatidylcholines. These are glycerophosphocholines in which the two free -OH are attached to one fatty acid each through an ester linkage.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Glycerophospholipids
Sub Class
Glycerophosphocholines
Direct Parent
Phosphatidylcholines
Alternative Parents
Phosphocholines / Fatty acid esters / Dialkyl phosphates / Dicarboxylic acids and derivatives / Tetraalkylammonium salts / Carboxylic acid esters / Organopnictogen compounds / Organic salts / Organic oxides / Hydrocarbon derivatives
show 2 more
Substituents
Aliphatic acyclic compound / Alkyl phosphate / Amine / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Diacylglycero-3-phosphocholine / Dialkyl phosphate / Dicarboxylic acid or derivatives / Fatty acid ester
show 14 more
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
phosphatidylcholine 32:0 (CHEBI:72999) / Diacylglycerophosphocholines (LMGP01010564)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
319X2NFW0A
CAS number
63-89-8
InChI Key
KILNVBDSWZSGLL-KXQOOQHDSA-N
InChI
InChI=1S/C40H80NO8P/c1-6-8-10-12-14-16-18-20-22-24-26-28-30-32-39(42)46-36-38(37-48-50(44,45)47-35-34-41(3,4)5)49-40(43)33-31-29-27-25-23-21-19-17-15-13-11-9-7-2/h38H,6-37H2,1-5H3/t38-/m1/s1
IUPAC Name
(2-{[(2R)-2,3-bis(hexadecanoyloxy)propyl phosphono]oxy}ethyl)trimethylazanium
SMILES
CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC

References

General References
  1. Bryson HM, Whittington R: Colfosceril palmitate. A pharmacoeconomic evaluation of a synthetic surfactant preparation (Exosurf Neonatal) in infants with respiratory distress syndrome. Pharmacoeconomics. 1994 Dec;6(6):563-77. [Article]
  2. Reynolds MS, Wallander KA: Use of surfactant in the prevention and treatment of neonatal respiratory distress syndrome. Clin Pharm. 1989 Aug;8(8):559-76. [Article]
  3. DeAngelis RL, Findlay JW: Metabolism of synthetic surfactants. Clin Perinatol. 1993 Dec;20(4):697-710. [Article]
  4. Jackson, J.C. (2012). Avery's diseases of the newborn (9th ed., pp. 633-646). Elsevier.
  5. Sweet D. and Speer C. (2012). The newborn lung: neonatology questions and controversies (2nd ed., pp. 283-299). Elsevier.
  6. 1. (2010). In Ashcraft's pediatric surgery (5th ed., pp. 3-18). Elsevier.
  7. 52. (2011). In Pediatric Critical Care (4th ed., pp. 706-716). Mosby.
  8. Pharmaintelligence [Link]
  9. Access [Link]
  10. Curoservice [Link]
  11. Rob Holland [Link]
Human Metabolome Database
HMDB0000564
PubChem Compound
452110
PubChem Substance
310265031
ChemSpider
398235
RxNav
69782
ChEBI
72999
ChEMBL
CHEMBL1200737
PDBe Ligand
PCF
Wikipedia
Colfosceril_palmitate
PDB Entries
1kb9 / 2azq / 2ygn / 2ygo / 2ygp / 2ygq / 5vkq / 6giq / 6hu9 / 6t0b …
show 10 more
MSDS
Download (161 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentHypoxemic Acute Respiratory Failure1
2TerminatedPreventionChronic Lung Disease of Prematurity / Premature Births / Respiratory Distress Syndrome, Newborn1
2, 3CompletedTreatmentChronic Lung Disease of Prematurity / Infants, Premature / Low Birth Weight Infants / Newborn, Infant / Small for Gestational Age Infants1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Kit; powder, for suspensionEndotracheal108 mg / vial
Powder, for suspensionEndotracheal108 mg / vial
SuspensionEndotracheal
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)-63ºC'MSDS'
boiling point (°C)60.5-61.5ºC at 760 mmHg'MSDS'
water solubilityVery poor solubilityLi, et al. Asian Journal of Pharmaceutical Sciences. Vol. 10. Issue 2. (2015)
logP1.97'MSDS'
Predicted Properties
PropertyValueSource
Water Solubility2.4e-05 mg/mLALOGPS
logP5.29ALOGPS
logP8.11Chemaxon
logS-7.5ALOGPS
pKa (Strongest Acidic)1.86Chemaxon
pKa (Strongest Basic)-6.7Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area111.19 Å2Chemaxon
Rotatable Bond Count40Chemaxon
Refractivity215.87 m3·mol-1Chemaxon
Polarizability92 Å3Chemaxon
Number of Rings0Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-326.2204665
predicted
DarkChem Lite v0.1.0
[M-H]-360.5823665
predicted
DarkChem Lite v0.1.0
[M-H]-347.0202587
predicted
DarkChem Lite v0.1.0
[M-H]-350.2565665
predicted
DarkChem Lite v0.1.0
[M-H]-279.44186
predicted
DeepCCS 1.0 (2019)
[M+H]+327.9420665
predicted
DarkChem Lite v0.1.0
[M+H]+357.6730665
predicted
DarkChem Lite v0.1.0
[M+H]+347.8702587
predicted
DarkChem Lite v0.1.0
[M+H]+348.8335665
predicted
DarkChem Lite v0.1.0
[M+H]+282.14536
predicted
DeepCCS 1.0 (2019)
[M+Na]+327.8714665
predicted
DarkChem Lite v0.1.0
[M+Na]+360.7980665
predicted
DarkChem Lite v0.1.0
[M+Na]+348.6772587
predicted
DarkChem Lite v0.1.0
[M+Na]+352.3280665
predicted
DarkChem Lite v0.1.0
[M+Na]+289.462
predicted
DeepCCS 1.0 (2019)

Drug created at September 22, 2015 16:07 / Updated at September 12, 2023 18:32