Fospropofol
Identification
- Summary
Fospropofol is a sedative-hypnotic agent indicated for monitored anesthesia care (MAC) sedation in adult patients undergoing diagnostic or therapeutic procedures.
- Generic Name
- Fospropofol
- DrugBank Accession Number
- DB06716
- Background
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. Fospropofol is a Schedule IV controlled substance in the United States under the Controlled Substances Act.
- Type
- Small Molecule
- Groups
- Approved, Illicit, Investigational
- Structure
Structure for Fospropofol (DB06716)
- Weight
- Average: 288.2766
Monoisotopic: 288.112660294 - Chemical Formula
- C13H21O5P
- Synonyms
- Fospropofol
- External IDs
- DEA No. 2138
- GPI 15715
Pharmacology
- Indication
For monitored anaesthesia care sedation in patients undergoing diagnostic procedures like bronchoscopy and colonscopy or minor surgical procedures like arthroscopy and bunionectomy.
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- 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.
Target Actions Organism AGamma-aminobutyric acid receptor subunit beta-2 potentiatorHumans AGamma-aminobutyric acid receptor subunit beta-3 potentiatorHumans - 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. Following an intravenous bolus administration of 6 mg/kg in a healthy subject, the pharmacokinetic parameters of fospropofol are as follows: Cmax = 78.7 μg/mL; Tmax = 4 minutes; AUC(0-∞) = 19.0 μg ⋅ h/mL;
- Volume of distribution
Fospropofol = 0.33±0.069 L/kg; Propofol metabolite = 5.8 L/kg.
- Protein binding
Both fospropofol and its active metabolite propofol are highly protein bound (approximately 98%), primarily to albumin. Fospropofol does not affect the binding of propofol 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. Propofol is further metabolized into propofol glucuronide, quinol-4-sulfate, quinol-1-fluronide, and quinol-4-glucuronide. The cytochrome P450 enzyme system is not involved with the metabolism of fospropofol.
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- 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
When given to a patient, the half-lives are as follows: Fospropofol = 0.81 hours; Propofol metabolite = 1.13 hours
- Clearance
Total body clearance (CLp), Fospropofol, healthy subject = 0.28 L/h/kg; CLp, fospropofol, patients = 0.31 L/h/kg; CLp/F, propofol, healthy subjects or patients = 2.74 L/h/kg.
- Adverse Effects
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Overdosage may lead to cardiorespiratory depression, formic acid toxicity (methanol toxicity-like effects), and/or phosphate-induced hypocalemia. Most common adverse reactions (> 20%) are paresthesia and pruritus.
- 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of adverse effects can be increased when Fospropofol is combined with 1,2-Benzodiazepine. Acetazolamide The risk or severity of adverse effects can be increased when Acetazolamide is combined with Fospropofol. Acetophenazine The risk or severity of adverse effects can be increased when Acetophenazine is combined with Fospropofol. Aclidinium Fospropofol may increase the central nervous system depressant (CNS depressant) activities of Aclidinium. Agomelatine The risk or severity of adverse effects can be increased when Agomelatine is combined with Fospropofol. Alfentanil The risk or severity of adverse effects can be increased when Alfentanil is combined with Fospropofol. Alimemazine The risk or severity of adverse effects can be increased when Alimemazine is combined with Fospropofol. Almotriptan The risk or severity of adverse effects can be increased when Almotriptan is combined with Fospropofol. Alosetron The risk or severity of adverse effects can be increased when Alosetron is combined with Fospropofol. Alprazolam The risk or severity of adverse effects can be increased when Alprazolam is combined with Fospropofol. 
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- Not Available
Products
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Ingredient UNII CAS InChI Key Fospropofol disodium 30868AY0IF 258516-87-9 LWYLQNWMSGFCOZ-UHFFFAOYSA-L - Active Moieties
Name Kind UNII CAS InChI Key Propofol prodrug YI7VU623SF 2078-54-8 OLBCVFGFOZPWHH-UHFFFAOYSA-N - International/Other Brands
- Aquavan
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Lusedra Injection 35 mg/1mL Intravenous Eisai Limited 2008-12-12 2012-07-31 US 
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as cumenes. These are aromatic compounds containing a prop-2-ylbenzene moiety.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Cumenes
- Direct Parent
- Cumenes
- Alternative Parents
- Phenylpropanes / Phenoxy compounds / Phenol ethers / Monoalkyl phosphates / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives
- Substituents
- Alkyl phosphate / Aromatic homomonocyclic compound / Cumene / Hydrocarbon derivative / Monoalkyl phosphate / Organic oxide / Organic oxygen compound / Organic phosphoric acid derivative / Organooxygen compound / Phenol ether
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- LZ257RZP7K
- CAS number
- 258516-89-1
- InChI Key
- QVNNONOFASOXQV-UHFFFAOYSA-N
- InChI
- InChI=1S/C13H21O5P/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)
- IUPAC Name
- [2,6-bis(propan-2-yl)phenoxymethoxy]phosphonic acid
- SMILES
- CC(C)C1=CC=CC(C(C)C)=C1OCOP(O)(O)=O
References
- General References
- Garnock-Jones KP, Scott LJ: Fospropofol. Drugs. 2010 Mar 5;70(4):469-77. doi: 10.2165/11204450-000000000-00000. [Article]
- 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. [Article]
- Bengalorkar GM, Bhuvana K, Sarala N, Kumar T: Fospropofol: clinical pharmacology. J Anaesthesiol Clin Pharmacol. 2011 Jan;27(1):79-83. [Article]
- 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. [Article]
- External Links
- Human Metabolome Database
- HMDB0015661
- KEGG Drug
- D04257
- PubChem Compound
- 3038498
- PubChem Substance
- 99443268
- ChemSpider
- 2302062
- 828682
- ChEBI
- 135193
- ChEMBL
- CHEMBL1201766
- ZINC
- ZINC000002519740
- PharmGKB
- PA165958389
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Fospropofol
- FDA label
- Download (536 KB)
- MSDS
- Download (479 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Anaesthesia therapy 1 4 Completed Treatment Complication of Injection / Pain 1 4 Completed Treatment Sedation 1 4 Terminated Treatment Orthopedic Procedures / Procedural Sedation / Regional Anesthesia Block 1 3 Completed Treatment Anaesthesia therapy / Bronchoscopy； 1 3 Completed Treatment Angioplasty / Coronary Catheterization 1 3 Completed Treatment Colon Polyps / Colonoscopy 1 3 Completed Treatment Sedation, Conscious 1 3 Terminated Treatment Arthroscopy / Bunionectomy / Carpal Tunnel / Osteotomy 1 3 Terminated Treatment Flexible Bronchoscopy 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 35 mg/1mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6204257 No 2001-03-20 2022-07-01 US US6872838 No 2005-03-29 2018-08-07 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source pKa 8.2 - 9.0 FDA label - Predicted Properties
Property Value Source Water Solubility 0.302 mg/mL ALOGPS logP 2.23 ALOGPS logP 3.6 ChemAxon logS -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 2 ChemAxon Polar Surface Area 75.99 Å2 ChemAxon Rotatable Bond Count 6 ChemAxon Refractivity 72.88 m3·mol-1 ChemAxon Polarizability 29 Å3 ChemAxon Number of Rings 1 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.5105 Blood Brain Barrier + 0.8462 Caco-2 permeable - 0.546 P-glycoprotein substrate Non-substrate 0.6735 P-glycoprotein inhibitor I Non-inhibitor 0.8244 P-glycoprotein inhibitor II Non-inhibitor 0.9747 Renal organic cation transporter Non-inhibitor 0.9124 CYP450 2C9 substrate Non-substrate 0.8021 CYP450 2D6 substrate Non-substrate 0.8086 CYP450 3A4 substrate Non-substrate 0.5052 CYP450 1A2 substrate Non-inhibitor 0.7667 CYP450 2C9 inhibitor Non-inhibitor 0.7807 CYP450 2D6 inhibitor Non-inhibitor 0.9205 CYP450 2C19 inhibitor Non-inhibitor 0.7375 CYP450 3A4 inhibitor Non-inhibitor 0.8538 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8754 Ames test Non AMES toxic 0.7212 Carcinogenicity Non-carcinogens 0.6902 Biodegradation Not ready biodegradable 0.7478 Rat acute toxicity 2.3516 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8892 hERG inhibition (predictor II) Non-inhibitor 0.926
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Potentiator
- General Function
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function
- Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...
- Gene Name
- GABRB2
- Uniprot ID
- P47870
- Uniprot Name
- Gamma-aminobutyric acid receptor subunit beta-2
- Molecular Weight
- 59149.895 Da
References
- Franks NP: Molecular targets underlying general anaesthesia. Br J Pharmacol. 2006 Jan;147 Suppl 1:S72-81. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Potentiator
- General Function
- Gaba-gated chloride ion channel activity
- Specific Function
- Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...
- Gene Name
- GABRB3
- Uniprot ID
- P28472
- Uniprot Name
- Gamma-aminobutyric acid receptor subunit beta-3
- Molecular Weight
- 54115.04 Da
References
- Franks NP: Molecular targets underlying general anaesthesia. Br J Pharmacol. 2006 Jan;147 Suppl 1:S72-81. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
Drug created on May 16, 2010 23:53 / Updated on October 07, 2021 12:08