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

Molecular Formula	Na
Molecular Weight	22.9898
Charge	1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C13H19O5P
Molecular Weight	286.2607
Charge	-2
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 202 Target ID: CHEMBL2093872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10637364	Modulator 828

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019627s045lbl.pdf	Primary		Approved 8429	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 1737 inhibitor 1587	substrate 1037 inhibitor 1767	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT1A9 116 UGT1A1 204 CYP2E1 882 CYP2B1 14 CYP1A1 110 CYP1A2 1524	CYP2B6 664 CYP1A2 1054 CYP2A6 543 CYP2C19 991 CYP2E1 667 UGT1A9 380

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9764927/	weak [IC50 213 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12970884/ \| https://pubmed.ncbi.nlm.nih.gov/9764927/	yes [IC50 32 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9764927/	yes [IC50 40 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9764927/	yes [IC50 49 uM]
UGT1A9 121	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15378558/	yes [IC50 55 uM]
UGT1A1 254	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17697043/	yes [IC50 59 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/7772432/ \| https://pubmed.ncbi.nlm.nih.gov/12234619/	yes [Ki 48 uM]
CYP1A1 218	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/7772432/	yes
CYP2B1 41	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/7772432/	yes
P-gp 1650	activator 214 Sources: https://pubmed.ncbi.nlm.nih.gov/17986257/	yes
UGT1A1 254	activator 214 Sources: https://pubmed.ncbi.nlm.nih.gov/17697043/	yes
UGT1A8 48	activator 214 Sources: https://pubmed.ncbi.nlm.nih.gov/15378558/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2C9 1037	substrate 3367 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 664	substrate 3367 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 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11135730/	minor
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11135730/	minor
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11135730/	minor
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11135730/	minor
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11135730/	minor
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11135730/	minor
UGT1A9 380	substrate 3367 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 1647	inhibitor 1626 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
ZINC	ZINC000000968303	http://zinc15.docking.org/substances/ZINC000000968303
eMolecules	536859	https://www.emolecules.com/cgi-bin/more?vid=536859

PubMed

Title	Date	PubMed
[Premixing of 5% dextrose in Ringer's acetate solution with propofol reduces incidence and severity of pain on propofol injection].	1999 Aug	10481420
[Effects of the bolus injection rate on anesthesia induction with propofol].	1999 Aug	10481418
[Effects of speed of injection on anesthesia induction with propofol and fentanyl].	1999 Aug	10481417
[Administration of propofol. Addition of lidocaine eases the pain].	1999 Jun	10514777
The haemodynamic effects of propofol in combination with ephedrine in elderly patients (ASA groups 3 and 4).	1999 Oct	10520387
Acute detoxification of opioid-addicted patients with naloxone during propofol or methohexital anesthesia: a comparison of withdrawal symptoms, neuroendocrine, metabolic, and cardiovascular patterns.	2000 Apr	10809268
Propofol-associated rhabdomyolysis with cardiac involvement in adults: chemical and anatomic findings.	2000 Apr	10759487
Renal responses to low-flow desflurane, sevoflurane, and propofol in patients.	2000 Dec	11149433
[Case of uncommon motor reaction to administration of diprivan].	2000 Jul-Aug	11014005
[Intra- and postoperative heart rate changes following propofol anesthesia; a comparison with isoflurane anesthesia].	2000 Jun	10885236
Prospective evaluation of propofol anesthesia in the pediatric intensive care unit for elective oncology procedures in ambulatory and hospitalized children.	2000 Oct	11015517
Midazolam-induced dyskinesia.	2000 Sep	11064794
[Preliminary report: the effect of flumazenil on the hypnotic dose of propofol in ddY mice].	2001 Feb	11244771
[Anesthetic management of two patients with insulinoma using propofol--in association with rapid radioimmunoassay for insulin].	2001 Feb	11244767
[Clinical evaluation of roxatidine acetate hydrochlorides as a preanesthetic medication].	2001 Feb	11244765
A randomized prospective comparative study of general versus epidural anesthesia for transcervical hysteroscopic endometrial resection.	2001 Feb	11228472
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
Effect of dexmedetomidine on propofol requirements in healthy subjects.	2001 Feb	11169534
Reversal of rocuronium with edrophonium during propofol versus sevoflurane anesthesia.	2001 Feb	11167172
Propofol anesthesia induces phase synchronization changes in EEG.	2001 Feb	11165545
The differential effect of propofol on contractility of isolated myocardial trabeculae of rat and guinea-pig.	2001 Feb	11159727
Propofol depressed neutrophil hydrogen peroxide production more than midazolam, whereas adhesion molecule expression was minimally affected by both anesthetics in rats with abdominal sepsis.	2001 Feb	11159247
The use of esmolol as an alternative to remifentanil during desflurane anesthesia for fast-track outpatient gynecologic laparoscopic surgery.	2001 Feb	11159231
Hyperintense signal abnormality in subarachnoid spaces and basal cisterns on MR images of children anesthetized with propofol: new fluid-attenuated inversion recovery finding.	2001 Feb	11156789
Propofol action in both spinal cord and brain blunts electroencephalographic responses to noxious stimulation in goats.	2001 Feb 1	11204050
[Epileptoform EEG activity: occurrence under sevoflurane and not during propofol application].	2001 Jan	11220258
High concentration sevoflurane induction of anesthesia accelerates onset of vecuronium neuromuscular blockade.	2001 Jan	11212046
Remifentanil and controlled hypotension; comparison with nitroprusside or esmolol during tympanoplasty.	2001 Jan	11212044
Dystonic reaction after anesthesia.	2001 Jan	11212039
[The Baxter AS 50 syringe pump: a comparison with propofol-specific syringe pumps].	2001 Jan	11211760
[Marked bradycardia during anesthetic induction treated with temporary cardiac pacing in a patient with latent sick sinus syndrome].	2001 Jan	11211756
[The influence of age on hemodynamics and the dose requirements of propofol and buprenorphine in total intravenous anesthesia].	2001 Jan	11211745
Differential roles of iNOS and nNOS at rostral ventrolateral medulla during experimental endotoxemia in the rat.	2001 Jan	11198360
Spectral changes in systemic arterial pressure signals during acute mevinphos intoxication in the rat.	2001 Jan	11198355
Target-controlled infusion in sleep endoscopy.	2001 Jan	11192890
Prevention of postoperative nausea and vomiting with antiemetics in patients undergoing middle ear surgery: comparison of a small dose of propofol with droperidol or metoclopramide.	2001 Jan	11177010
Effect of dexmedetomidine, an alpha2-adrenoceptor agonist, on human pupillary reflexes during general anaesthesia.	2001 Jan	11167662
Digitally assisted acromioplasty: the effect of interscalene block on this new surgical technique.	2001 Jan	11154366
Myopexy (Faden) results in more postoperative vomiting after strabismus surgery in children.	2001 Jan	11152035
Cytochrome P-450 2B6 is responsible for interindividual variability of propofol hydroxylation by human liver microsomes.	2001 Jan	11135730
Effects of propofol on H-reflex in humans.	2001 Jan	11135719
Direct current auditory evoked potentials during wakefulness, anesthesia, and emergence from anesthesia.	2001 Jan	11133619
Awake craniotomy for removal of intracranial tumor: considerations for early discharge.	2001 Jan	11133607
Dexamethasone facilitates discharge after outpatient anorectal surgery.	2001 Jan	11133606
The efficacy of oral clonidine premedication in the prevention of postoperative vomiting in children following strabismus surgery.	2001 Jan	11123735
Fibreoptic nasal intubation in children with anticipated and unanticipated difficult intubation.	2001 Jan	11123731
Extracranial radiosurgery: immobilizing liver motion in dogs using high-frequency jet ventilation and total intravenous anesthesia.	2001 Jan 1	11163517
Long-term propofol infusion and cardiac failure in adult head-injured patients.	2001 Jan 13	11197401

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

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:17:19 GMT 2023` Edited by `admin` on `Fri Dec 15 16:17:19 GMT 2023`
Record UNII	30868AY0IF
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FOSPROPOFOL DISODIUM

Official 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

FOSPROPOFOL SODIUM

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C245