Identification

Name

Fospropofol

Accession Number

DB06716

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. Fospropofol is a Schedule IV controlled substance in the United States under the Controlled Substances Act.

Type

Small Molecule

Groups

Approved, Illicit, Investigational

Structure

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Fospropofol (DB06716)

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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.

Associated Therapies

• Monitored anesthesia care sedation

Contraindications & Blackbox Warnings

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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	potentiator	Humans
AGamma-aminobutyric acid receptor subunit beta-3	potentiator	Humans

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.

Hover over products below to view reaction partners

• Fospropofol
  • Formic acid
  • Formaldehyde
  • Phosphate
  • Propofol

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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Toxicity

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.

Affected organisms

• Humans and other mammals

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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
Unlock Additional Data
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.
Alverine	The risk or severity of adverse effects can be increased when Alverine is combined with Fospropofol.

Additional Data Available

Extended Description
Extended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
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Severity
Severity
A severity rating for each drug interaction, from minor to major.
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Evidence Level
Evidence Level
A rating for the strength of the evidence supporting each drug interaction.
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Action
Action
An effect category for each drug interaction. Know how this interaction affects the subject drug.
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Food Interactions

Not Available

Products

Product Ingredients

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
Unlock Additional Data
Lusedra	Injection	35 mg/1mL	Intravenous	Eisai Limited	2008-12-12	2012-07-31

Additional Data Available

Application Number
Application Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
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Product Code
Product Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Categories

Drug Categories

• Agents that reduce seizure threshold
• Anesthetics
• Anesthetics, General
• Benzene Derivatives
• Central Nervous System Agents
• Central Nervous System Depressants
• Hypnotics and Sedatives
• Phenols

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

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

1. Garnock-Jones KP, Scott LJ: Fospropofol. Drugs. 2010 Mar 5;70(4):469-77. doi: 10.2165/11204450-000000000-00000. [PubMed:20205488]
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:12650488]
3. Bengalorkar GM, Bhuvana K, Sarala N, Kumar T: Fospropofol: clinical pharmacology. J Anaesthesiol Clin Pharmacol. 2011 Jan;27(1):79-83. [PubMed:21804712]
4. 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:22584560]

External Links

Human Metabolome Database

HMDB0015661

KEGG Drug

D04257

PubChem Compound

3038498

PubChem Substance

99443268

ChemSpider

2302062

RxNav

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
Unlock Additional Data
US6204257	No	2001-03-20	2022-07-01
US6872838	No	2005-03-29	2018-08-07

Additional Data Available

Filed On
Filed On
The date on which a patent was filed with the relevant government.
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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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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

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Drug created on May 16, 2010 17:53 / Updated on June 12, 2020 11:41