FOSPROPOFOL DISODIUM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H19O5P.2Na
Molecular Weight	332.2403
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].[Na+].CC(C)C1=CC=CC(C(C)C)=C1OCOP([O-])([O-])=O

InChI

InChIKey=LWYLQNWMSGFCOZ-UHFFFAOYSA-L

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

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10637364
Curator's Comment: description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019627s045lbl.pdf https://www.ncbi.nlm.nih.gov/pubmed/12665397

Propofol (2,6-diisopropylphenol) is an intravenous anaesthetic agent used for induction and maintenance of general anaesthesia. IV administration of propfol is used to induce unconsciousness after which anaesthesia may be maintained using a combination of medications. It is extensively metabolized, with most of the administered dose appearing in the urine as glucuronide conjugates. Favorable operating conditions and rapid recovery are claimed as the main advantages in using propofol, whereas disadvantages include a relatively high incidence of apnea, and blood pressure reductions. The action of propofol involves a positive modulation of the inhibitory function of the neurotransmitter gama-aminobutyric acid (GABA) through GABA-A receptors. Due to its high lipid-solubility, propofol was initially formulated as a solution with the surfactant Cremophor EL, but the occurrence of pain on injection and anaphylactoid reactions prompted to search for alternative formulations. Results from using cyclodextrins, water-soluble prodrugs, and adopting Bodor's approach to the site-specific chemical delivery system (CDS), as well as the advantages provided by computer-controlled infusion systems, are examined in some detail.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; anion channel 203 Target ID: CHEMBL2093872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10637364	Modulator 846

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 619 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019627s045lbl.pdf	Primary		Approved 8583	DIPRIVAN Approved Use Propofol injectable emulsion is an I.V. sedative-hypnotic agent that can be used as described in the table below. TABLE 3. INDICATIONS FOR PROPOFOL INJECTABLE EMULSION Indication Approved Patient Population Initiation and maintenance of Monitored Anesthesia Care (MAC) sedation Adults only Combined sedation and regional anesthesia Adults only (See PRECAUTIONS ) Induction of General Anesthesia Patients ≥ 3 years of age Maintenance of General Anesthesia Patients ≥ 2 months of age Intensive Care Unit (ICU) sedation of intubated, mechanically ventilated patients Adults only Safety, effectiveness and dosing guidelines for propofol injectable emulsion have not been established for MAC Sedation in the pediatric population; therefore, it is not recommended for this use. (See PRECAUTIONS - Pediatric Use.) Propofol injectable emulsion is not recommended for induction of anesthesia below the age of 3 years or for maintenance of anesthesia below the age of 2 months because its safety and effectiveness have not been established in those populations. In the Intensive Care Unit (ICU), propofol injectable emulsion can be administered to intubated, mechanically ventilated adult patients to provide continuous sedation and control of stress responses, only by persons skilled in the medical management of critically ill patients and trained in cardiovascular resuscitation and airway management. Propofol injectable emulsion is not indicated for use in Pediatric ICU sedation since the safety of this regimen has not been established. (See PRECAUTIONS - Pediatric Use.) Propofol injectable emulsion is not recommended for obstetrics, including Cesarean section deliveries. Propofol injectable emulsion crosses the placenta, and as with other general anesthetic agents, the administration of propofol injectable emulsion may be associated with neonatal depression. (See PRECAUTIONS .) Propofol is not recommended for use in nursing mothers because propofol injectable emulsion has been reported to be excreted in human milk and the effects of oral absorption of small amounts of propofol are not known. (See PRECAUTIONS .) Launch Date 1989

C_max

Value	Dose	Co-administered	Analyte	Population
3.854 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11753007	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		PROPOFOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1.183 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11753007	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		PROPOFOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.43 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11753007	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		PROPOFOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	substrate 1193 inhibitor 2438	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT1A9 148 UGT1A1 246 CYP2E1 1060 CYP2B1 14 CYP1A1 132 CYP1A2 2153	CYP2B6 776 CYP1A2 1197 CYP2A6 626 CYP2C19 1119 CYP2E1 729 UGT1A9 423

Drug as perpetrator

Target	Modality	Activity
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/9764927/	weak [IC50 213 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12970884/ \| https://pubmed.ncbi.nlm.nih.gov/9764927/	yes [IC50 32 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/9764927/	yes [IC50 40 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/9764927/	yes [IC50 49 uM]
UGT1A9 155	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/15378558/	yes [IC50 55 uM]
UGT1A1 303	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17697043/	yes [IC50 59 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/7772432/ \| https://pubmed.ncbi.nlm.nih.gov/12234619/	yes [Ki 48 uM]
CYP1A1 272	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/7772432/	yes
CYP2B1 41	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/7772432/	yes
P-gp 1932	activator 342 Sources: https://pubmed.ncbi.nlm.nih.gov/17986257/	yes
UGT1A1 303	activator 342 Sources: https://pubmed.ncbi.nlm.nih.gov/17697043/	yes
UGT1A8 49	activator 342 Sources: https://pubmed.ncbi.nlm.nih.gov/15378558/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11135730/	major	no (pharmacogenomic study) Comment: polymorphisms c.98T>C in the UGT1A9 and c.1075A>C in the CYP2C9 genes did not affect the pharmacokinetic profile of propofol Sources: https://pubmed.ncbi.nlm.nih.gov/11135730/
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/27826892/ \| https://pubmed.ncbi.nlm.nih.gov/26141406/ \| https://pubmed.ncbi.nlm.nih.gov/11135730/	major	yes (pharmacogenomic study) Comment: only polymorphism c.516G>T in the CYP2B6 gene and BMI affect the metabolism rate of propofol and may play an important role in the optimisation of propofol anaesthesia Sources: https://pubmed.ncbi.nlm.nih.gov/27826892/ \| https://pubmed.ncbi.nlm.nih.gov/26141406/ \| https://pubmed.ncbi.nlm.nih.gov/11135730/
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11135730/	minor
CYP2A6 626	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11135730/	minor
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11135730/	minor
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11135730/	minor
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11135730/	minor
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11135730/	minor
UGT1A9 423	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/18816295/ \| https://pubmed.ncbi.nlm.nih.gov/20828969/	yes	no (pharmacogenomic study) Comment: polymorphisms c.98T>C in the UGT1A9 and c.1075A>C in the CYP2C9 genes did not affect the pharmacokinetic profile of propofol Sources: https://pubmed.ncbi.nlm.nih.gov/18816295/ \| https://pubmed.ncbi.nlm.nih.gov/20828969/

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/27575519/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:44915	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:44915
ChemicalBook	CB4101882	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4101882
eMolecules	536859	https://www.emolecules.com/cgi-bin/more?vid=536859
ZINC	ZINC000000968303	http://zinc15.docking.org/substances/ZINC000000968303

PubMed

Title	Date	PubMed
Heart block following propofol in a child.	1999	10411774
[Administration of propofol. Addition of lidocaine eases the pain].	1999 Jun	10514777
[Erotic hallucinations associated with the use of propofol].	2000 Feb	10769556
The effects of pentobarbital, isoflurane, and propofol on immediate-early gene expression in the vital organs of the rat.	2000 May	10781476
A randomized prospective comparative study of general versus epidural anesthesia for transcervical hysteroscopic endometrial resection.	2001 Feb	11228472
Propofol in subanesthetic doses terminates status epilepticus in a rodent model.	2001 Feb	11220748
Timing of pre-emptive tenoxicam is important for postoperative analgesia.	2001 Feb	11220425
High concentrations of isoflurane do not block the sympathetic nervous system activation from desflurane.	2001 Feb	11220421
Evaluation of the effective drugs for the prevention of nausea and vomiting induced by morphine used for postoperative pain: a quantitative systematic review.	2001 Feb	11218733
Evidence for significant differences in microsomal drug glucuronidation by canine and human liver and kidney.	2001 Feb	11159800
The differential effect of propofol on contractility of isolated myocardial trabeculae of rat and guinea-pig.	2001 Feb	11159727
Chronic mu-opioid receptor stimulation in humans decreases muscle sympathetic nerve activity.	2001 Feb 13	11171794
[Epileptoform EEG activity: occurrence under sevoflurane and not during propofol application].	2001 Jan	11220258
Awake craniotomy for removal of intracranial tumor: considerations for early discharge.	2001 Jan	11133607
Extracranial radiosurgery: immobilizing liver motion in dogs using high-frequency jet ventilation and total intravenous anesthesia.	2001 Jan 1	11163517
Use of the Bispectral Index monitor to aid titration of propofol during a drug-assisted interview.	2001 Mar	11240887
Anaesthetic technique for transoesophageal echocardiography in children.	2001 Mar	11240876
Propofol is not effective for hyperventilation syndrome.	2001 Mar	11226118
The effect of the preemptive use of the NMDA receptor antagonist dextromethorphan on postoperative analgesic requirements.	2001 Mar	11226111
The determinants of propofol induction of anesthesia dose.	2001 Mar	11226096
Evaluation of the safety and efficacy of repeated sedations for the radiotherapy of young children with cancer: a prospective study of 1033 consecutive sedations.	2001 Mar 1	11172961

Patents

Sample Use Guides

In Vivo Use Guide

Adult Patients: Most adult patients under 55 years of age and classified as ASA-PS I or II require 2 to 2.5 mg/kg of DIPRIVAN ((propofol) Injectable Emulsion ) for induction when unpremedicated or when premedicated with oral benzodiazepines or intramuscular opioids. Elderly, Debilitated, or ASA-PS III or IV Patients: most of these patients require approximately 1 to 1.5 mg/kg (approximately 20 mg every 10 seconds) of DIPRIVAN Injectable Emulsion for induction of anesthesia according to their condition and responses. Pediatric Patients: Most patients aged 3 years through 16 years and classified ASA-PS I or II require 2.5 to 3.5 mg/kg of DIPRIVAN Injectable Emulsion for induction when unpremedicated or when lightly premedicated with oral benzodiazepines or intramuscular opioids

Route of Administration: Intravenous

In Vitro Use Guide

Propofol-induced cell (25, 50, and 100 µmol/L concentration of propofol) migration and invasion suppression are partially mediated by down-regulating H19 in MDA-MB-231 cells in vitro

Name

Type

Language

FOSPROPOFOL DISODIUM

Official Name

English

FOSPROPOFOL SODIUM

Preferred Name

English

AQUAVAN

Brand Name

English

FOSPROPOFOL DISODIUM [VANDF]

Common Name

English

METHANOL, (2,6-BIS(1-METHYLETHYL)PHENOXY)-, DIHYDROGEN PHOSPHATE, DISODIUM SALT

Common Name

English

FOSPROPOFOL SODIUM [MART.]

Common Name

English

FOSPROPOFOL DISODIUM SALT

Common Name

English

FOSPROPOFOL DISODIUM [ORANGE BOOK]

Common Name

English

FOSPROPOFOL DISODIUM [USAN]

Common Name

English

FOSPROPOFOL DISODIUM SALT [MI]

Common Name

English

[2,6-Bis(1-methylethyl)phenoxy]methyl disodium phosphate

Common Name

English

Fospropofol sodium [WHO-DD]

Common Name

English

2,6-DIISOPROPYLPHENOXYMETHYL PHOSPHATE,DISODIUM SALT

Common Name

English

LUSEDRA

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C245