FOSPROPOFOL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H21O5P
Molecular Weight	288.2766
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C1=CC=CC(C(C)C)=C1OCOP(O)(O)=O

InChI

InChIKey=QVNNONOFASOXQV-UHFFFAOYSA-N

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)

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 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
[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
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
Anesthetic concentrations of propofol protect against oxidative stress in primary astrocyte cultures: comparison with hypothermia.	2001 Feb	11176097
Assessment of depth of anesthesia and postoperative respiratory recovery after remifentanil- versus alfentanil-based total intravenous anesthesia in patients undergoing ear-nose-throat surgery.	2001 Feb	11176083
Relation between initial blood distribution volume and propofol induction dose requirement.	2001 Feb	11176082
Effect of dexmedetomidine on propofol requirements in healthy subjects.	2001 Feb	11169534
Effect of midazolam pretreatment on induction dose requirements of propofol in combination with fentanyl in younger and older adults.	2001 Feb	11167469
Reversal of rocuronium with edrophonium during propofol versus sevoflurane anesthesia.	2001 Feb	11167172
Effects of different preparations of propofol, diazepam, and etomidate on human neutrophils in vitro.	2001 Feb	11167168
Propofol anesthesia induces phase synchronization changes in EEG.	2001 Feb	11165545
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
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
Propofol action in both spinal cord and brain blunts electroencephalographic responses to noxious stimulation in goats.	2001 Feb 1	11204050
The effects of propofol on NMDA- or nitric oxide-mediated neurotoxicity in vitro.	2001 Feb 12	11209938
Chronic mu-opioid receptor stimulation in humans decreases muscle sympathetic nerve activity.	2001 Feb 13	11171794
[Hemodynamic effects of propofol induction administered with target controlled infusion pump in patients scheduled for open heart surgery].	2001 Feb 18	11243014
[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
[A case of hyperperfusion syndrome treated successfully by propofol].	2001 Jan	11211744
Propofol versus midazolam regarding their antioxidant activities.	2001 Jan	11208621
Does the use of propofol require a specialist anesthetist?	2001 Jan	11204998
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
The immunomodulatory effects of prolonged intravenous infusion of propofol versus midazolam in critically ill surgical patients.	2001 Jan	11167428
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
Small doses of propofol, droperidol, and metoclopramide for the prevention of postoperative nausea and vomiting after thyroidectomy.	2001 Mar	11240988
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
Recovery profile and side effects of remifentanil-based anaesthesia with desflurane or propofol for laparoscopic cholecystectomy.	2001 Mar	11207468
Reduced isoflurane consumption with bispectral index monitoring.	2001 Mar	11207466
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

Official Name

English

fospropofol [INN]

Common Name

English

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

Common Name

English

Fospropofol [WHO-DD]

Common Name

English

FOSPROPOFOL [MI]

Common Name

English

FOSPROPOFOL [VANDF]

Common Name

English

Classification Tree Code System Code

LIVERTOX

442