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Identification
Name Fospropofol
Accession Number DB06716 (DB05279)
Type small molecule
Groups approved
Description

Fospropofol is a water soluble prodrug and is converted to propofol in the liver. Fospropofol is a short acting hypnotic/sedative/anesthetic agent. Unlike propofol, does not cause injection-site pain as it is unable to activate TRPA1. FDA approved in December 2008.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Aquavan
GPI 15715
Salts
  • Fospropofol Disodium
Brand names
Name Company
Lusedra Eisai Inc.
Brand mixtures Not Available
Categories
  • Sedative
CAS number 258516-87-9
Weight Average: 332.2403
Monoisotopic: 332.07654958
Chemical Formula C13H19Na2O5P
InChI Key InChIKey=LWYLQNWMSGFCOZ-UHFFFAOYSA-L
InChI
InChI=1S/C13H21O5P.2Na/c1-9(2)11-6-5-7-12(10(3)4)13(11)17-8-18-19(14,15)16;;/h5-7,9-10H,8H2,1-4H3,(H2,14,15,16);;/q;2*+1/p-2
Plain Text
IUPAC Name
disodium 2,6-bis(propan-2-yl)phenoxymethyl phosphate
SMILES
[Na+].[Na+].CC(C)C1=CC=CC(C(C)C)=C1OCOP([O-])([O-])=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenols and Derivatives
  • Cumenes and Derivatives
  • Anisoles
Substructures
  • Anions
  • Phenols and Derivatives
  • Organophosphate Esters
  • Ethers
  • Benzene and Derivatives
  • Cumenes and Derivatives
  • Aromatic compounds
  • Anisoles
  • Phosphinic Acids and Derivatives
  • Phenyl Esters
  • Cations
Pharmacology
Indication For monitored anaesthesia care sedation in patients undergoing diagnostic procedures like bronchoscopy and colonscopy or minor surgical procedures like arthroscopy and bunionectomy.
Pharmacodynamics Fospropofol is a prodrug of propofol, a sedative hypnotic drug. Unlike propofol, fospropofol is water soluble and can be administered in an aqueous solution. 1.86 mg of fospropofol is the molar equivalent for 1mg of propofol.
Mechanism of action After in-vivo conversion of fospropofol into propofol by endothelial alkaline phosphatase, propofol crosses the blood-brain barrier, binds to GABA-A receptors and acts as an agonist. By binding to GABA-A receptor, it will cause an increase in chloride conductance, thus inhibiting the firing of new action potentials in the post-synaptic neuron.
Absorption Adequate sedation achieved after 7 minutes with a IV bolus dose of 10mg/kg. It takes 21-45 minutes for patients to recover for fospropopol-induced sedation. Cmax, fospropofol 6mg/kg = 78.7 μg/mL; AUC∞, fospropofol 6.5 mg/kg = 19.0 μg ⋅ h/mL
Volume of distribution

Fospropofol: 0.33±0.069 L/kg
Protein binding 98%, mainly to albumin
Metabolism Fospropofol is metabolized into propofol, formaldehyde, and phosphate by endothelial alkaline phosphatase. The metabolite, formaldehyde, is quickly oxidized into formic acid by glutathione dependent and independent dehydrogenases and erythrocytes. Excess formic acid is eliminated via oxidation to carbon dioxide through the tetrahydrofolate pathway. Fospropofol is not a CYP450 substrate.
Route of elimination Chiefly eliminated by hepatic conjugation to inactive metabolites which are excreted by the kidney. There is negligible renal elimination of unchanged fospropofol (<0.02%).
Half life Fospropofol: 46 minutes
Clearance

Fospropofol: 0.36 L/h/kg
Toxicity Overdosage may lead to cardiorespiratory depression, formic acid toxicity (methanol toxicity-like effects), and/or phosphate-induced hypocalemia.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Eisai inc
Packagers Not Available
Dosage forms
Form Route Strength
Injection, solution Intravenous 35 mg/mL
Prices Not Available
Patents
Country Patent Number Approved Expires (estimated)
United States 6204257 1998-06-07 2018-06-07
Properties
State solid
Experimental Properties Not Available
Predicted Properties
Property Value Source
water solubility 1.71e+00 g/l ALOGPS
logP 3.31 ALOGPS
logP 3.6 ChemAxon
logS -2.3 ALOGPS
pKa (strongest acidic) 1.44 ChemAxon
pKa (strongest basic) -5 ChemAxon
physiological charge -2 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 81.65 ChemAxon
rotatable bond count 6 ChemAxon
refractivity 70.63 ChemAxon
polarizability 28.49 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Garnock-Jones KP, Scott LJ: Fospropofol. Drugs. 2010 Mar 5;70(4):469-77. doi: 10.2165/11204450-000000000-00000. Pubmed
  2. Schywalsky M, Ihmsen H, Tzabazis A, Fechner J, Burak E, Vornov J, Schwilden H: Pharmacokinetics and pharmacodynamics of the new propofol prodrug GPI 15715 in rats. Eur J Anaesthesiol. 2003 Mar;20(3):182-90. Pubmed
  3. Bengalorkar GM, Bhuvana K, Sarala N, Kumar T: Fospropofol: clinical pharmacology. J Anaesthesiol Clin Pharmacol. 2011 Jan;27(1):79-83. Pubmed
  4. Garnock-Jones KP, Scott LJ: Fospropofol. Drugs. 2010 Mar 5;70(4):469-77. doi: 10.2165/11204450-000000000-00000. Pubmed
  5. Patwardhan A, Edelmayer R, Annabi E, Price T, Malan P, Dussor G: Receptor specificity defines algogenic properties of propofol and fospropofol. Anesth Analg. 2012 Oct;115(4):837-40. Epub 2012 May 14. Pubmed
External Links
Resource Link
KEGG Drug D04257 Link_out
PubChem Compound 3038497 Link_out
PubChem Substance 99443268 Link_out
PharmGKB PA165958389 Link_out
RxList http://www.rxlist.com/lusedra-drug.htm Link_out
Drugs.com http://www.drugs.com/ppa/fospropofol.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Fospropofol Link_out
ATC Codes
  • N01AX10
AHFS Codes
  • 28:04.92
PDB Entries Not Available
FDA label show (536 KB)
MSDS show (479 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Gamma-aminobutyric-acid receptor subunit beta-2

Pharmacological action: yes
Actions: potentiator

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: P47870 Link_out
Gene: GABRB2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Franks NP: Molecular targets underlying general anaesthesia. Br J Pharmacol. 2006 Jan;147 Suppl 1:S72-81. Pubmed

2. Gamma-aminobutyric-acid receptor subunit beta-3

Pharmacological action: yes
Actions: potentiator

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: P28472 Link_out
Gene: GABRB3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Franks NP: Molecular targets underlying general anaesthesia. Br J Pharmacol. 2006 Jan;147 Suppl 1:S72-81. Pubmed
Enzymes

1. Alkaline phosphatase, tissue-nonspecific isozyme

Actions: substrate

This isozyme may play a role in skeletal mineralization

UniProt ID: P05186 Link_out
Gene: ALPL Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bergese SD, Dalal P, Vandse R, Satlin A, Lin Z, Candiotti K, Cohen L, Gan TJ: A double-blind, randomized, multicenter, dose-ranging study to evaluate the safety and efficacy of fospropofol disodium as an intravenous sedative for colonoscopy in high-risk populations. Am J Ther. 2013 Mar;20(2):163-71. doi: 10.1097/MJT.0b013e318256ecfc. Pubmed
Comments
Drug created on May 16, 2010 17:53 / Updated on March 30, 2013 17:06