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Details

Stereochemistry ACHIRAL
Molecular Formula C13H21O5P
Molecular Weight 288.2771
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FOSPROPOFOL

SMILES

CC(C)c1cccc(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

Molecular Formula C13H21O5P
Molecular Weight 288.2771
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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

Curator's Comment:: Formulated as an oil-in-water emulsion for intravenous use, it is highly lipophilic and rapidly crosses the blood-brain barrier resulting in a rapid onset of action.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

6.2328963E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.854 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
1.183 ng × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.43 h
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
OverviewDrug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
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
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
minor
minor
minor
minor
minor
minor
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
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
[Preliminary report: the effect of flumazenil on the hypnotic dose of propofol in ddY mice].
2001 Feb
[Anesthetic management of two patients with insulinoma using propofol--in association with rapid radioimmunoassay for insulin].
2001 Feb
[Clinical evaluation of roxatidine acetate hydrochlorides as a preanesthetic medication].
2001 Feb
A randomized prospective comparative study of general versus epidural anesthesia for transcervical hysteroscopic endometrial resection.
2001 Feb
Propofol in subanesthetic doses terminates status epilepticus in a rodent model.
2001 Feb
Timing of pre-emptive tenoxicam is important for postoperative analgesia.
2001 Feb
High concentrations of isoflurane do not block the sympathetic nervous system activation from desflurane.
2001 Feb
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
Anesthetic concentrations of propofol protect against oxidative stress in primary astrocyte cultures: comparison with hypothermia.
2001 Feb
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
Relation between initial blood distribution volume and propofol induction dose requirement.
2001 Feb
Effect of dexmedetomidine on propofol requirements in healthy subjects.
2001 Feb
Effect of midazolam pretreatment on induction dose requirements of propofol in combination with fentanyl in younger and older adults.
2001 Feb
Reversal of rocuronium with edrophonium during propofol versus sevoflurane anesthesia.
2001 Feb
Effects of different preparations of propofol, diazepam, and etomidate on human neutrophils in vitro.
2001 Feb
Propofol anesthesia induces phase synchronization changes in EEG.
2001 Feb
Evidence for significant differences in microsomal drug glucuronidation by canine and human liver and kidney.
2001 Feb
The differential effect of propofol on contractility of isolated myocardial trabeculae of rat and guinea-pig.
2001 Feb
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
The use of esmolol as an alternative to remifentanil during desflurane anesthesia for fast-track outpatient gynecologic laparoscopic surgery.
2001 Feb
Propofol action in both spinal cord and brain blunts electroencephalographic responses to noxious stimulation in goats.
2001 Feb 1
The effects of propofol on NMDA- or nitric oxide-mediated neurotoxicity in vitro.
2001 Feb 12
Chronic mu-opioid receptor stimulation in humans decreases muscle sympathetic nerve activity.
2001 Feb 13
[Hemodynamic effects of propofol induction administered with target controlled infusion pump in patients scheduled for open heart surgery].
2001 Feb 18
[Epileptoform EEG activity: occurrence under sevoflurane and not during propofol application].
2001 Jan
High concentration sevoflurane induction of anesthesia accelerates onset of vecuronium neuromuscular blockade.
2001 Jan
Remifentanil and controlled hypotension; comparison with nitroprusside or esmolol during tympanoplasty.
2001 Jan
Dystonic reaction after anesthesia.
2001 Jan
[The Baxter AS 50 syringe pump: a comparison with propofol-specific syringe pumps].
2001 Jan
[Marked bradycardia during anesthetic induction treated with temporary cardiac pacing in a patient with latent sick sinus syndrome].
2001 Jan
[The influence of age on hemodynamics and the dose requirements of propofol and buprenorphine in total intravenous anesthesia].
2001 Jan
[A case of hyperperfusion syndrome treated successfully by propofol].
2001 Jan
Propofol versus midazolam regarding their antioxidant activities.
2001 Jan
Does the use of propofol require a specialist anesthetist?
2001 Jan
Differential roles of iNOS and nNOS at rostral ventrolateral medulla during experimental endotoxemia in the rat.
2001 Jan
Spectral changes in systemic arterial pressure signals during acute mevinphos intoxication in the rat.
2001 Jan
Target-controlled infusion in sleep endoscopy.
2001 Jan
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
Effect of dexmedetomidine, an alpha2-adrenoceptor agonist, on human pupillary reflexes during general anaesthesia.
2001 Jan
The immunomodulatory effects of prolonged intravenous infusion of propofol versus midazolam in critically ill surgical patients.
2001 Jan
Extracranial radiosurgery: immobilizing liver motion in dogs using high-frequency jet ventilation and total intravenous anesthesia.
2001 Jan 1
Long-term propofol infusion and cardiac failure in adult head-injured patients.
2001 Jan 13
Small doses of propofol, droperidol, and metoclopramide for the prevention of postoperative nausea and vomiting after thyroidectomy.
2001 Mar
Use of the Bispectral Index monitor to aid titration of propofol during a drug-assisted interview.
2001 Mar
Anaesthetic technique for transoesophageal echocardiography in children.
2001 Mar
The effect of the preemptive use of the NMDA receptor antagonist dextromethorphan on postoperative analgesic requirements.
2001 Mar
The determinants of propofol induction of anesthesia dose.
2001 Mar
Recovery profile and side effects of remifentanil-based anaesthesia with desflurane or propofol for laparoscopic cholecystectomy.
2001 Mar
Reduced isoflurane consumption with bispectral index monitoring.
2001 Mar
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
Patents

Sample Use Guides

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
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 Sat Jun 26 04:36:41 UTC 2021
Edited
by admin
on Sat Jun 26 04:36:41 UTC 2021
Record UNII
LZ257RZP7K
Record Status Validated (UNII)
Record Version
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Name Type Language
FOSPROPOFOL
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
FOSPROPOFOL [INN]
Common Name English
METHANOL, (2,6-BIS(1-METHYLETHYL)PHENOXY)-, DIHYDROGEN PHOSPHATE
Common Name English
FOSPROPOFOL [MI]
Common Name English
FOSPROPOFOL [VANDF]
Common Name English
FOSPROPOFOL [WHO-DD]
Common Name English
Classification Tree Code System Code
LIVERTOX 442
Created by admin on Sat Jun 26 04:36:41 UTC 2021 , Edited by admin on Sat Jun 26 04:36:41 UTC 2021
DEA NO. 2138
Created by admin on Sat Jun 26 04:36:41 UTC 2021 , Edited by admin on Sat Jun 26 04:36:41 UTC 2021
NCI_THESAURUS C29756
Created by admin on Sat Jun 26 04:36:41 UTC 2021 , Edited by admin on Sat Jun 26 04:36:41 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C76954
Created by admin on Sat Jun 26 04:36:41 UTC 2021 , Edited by admin on Sat Jun 26 04:36:41 UTC 2021
PRIMARY
DRUG BANK
DB06716
Created by admin on Sat Jun 26 04:36:41 UTC 2021 , Edited by admin on Sat Jun 26 04:36:41 UTC 2021
PRIMARY
FDA UNII
LZ257RZP7K
Created by admin on Sat Jun 26 04:36:41 UTC 2021 , Edited by admin on Sat Jun 26 04:36:41 UTC 2021
PRIMARY
CAS
258516-89-1
Created by admin on Sat Jun 26 04:36:41 UTC 2021 , Edited by admin on Sat Jun 26 04:36:41 UTC 2021
PRIMARY
MERCK INDEX
M5556
Created by admin on Sat Jun 26 04:36:41 UTC 2021 , Edited by admin on Sat Jun 26 04:36:41 UTC 2021
PRIMARY Merck Index
IUPHAR
7475
Created by admin on Sat Jun 26 04:36:41 UTC 2021 , Edited by admin on Sat Jun 26 04:36:41 UTC 2021
PRIMARY
PUBCHEM
3038498
Created by admin on Sat Jun 26 04:36:41 UTC 2021 , Edited by admin on Sat Jun 26 04:36:41 UTC 2021
PRIMARY
WIKIPEDIA
FOSPROPOFOL
Created by admin on Sat Jun 26 04:36:41 UTC 2021 , Edited by admin on Sat Jun 26 04:36:41 UTC 2021
PRIMARY
RXCUI
828682
Created by admin on Sat Jun 26 04:36:41 UTC 2021 , Edited by admin on Sat Jun 26 04:36:41 UTC 2021
PRIMARY RxNorm
INN
8696
Created by admin on Sat Jun 26 04:36:41 UTC 2021 , Edited by admin on Sat Jun 26 04:36:41 UTC 2021
PRIMARY
LACTMED
Fospropofol
Created by admin on Sat Jun 26 04:36:41 UTC 2021 , Edited by admin on Sat Jun 26 04:36:41 UTC 2021
PRIMARY
ChEMBL
CHEMBL1201766
Created by admin on Sat Jun 26 04:36:41 UTC 2021 , Edited by admin on Sat Jun 26 04:36:41 UTC 2021
PRIMARY
DRUG CENTRAL
3249
Created by admin on Sat Jun 26 04:36:41 UTC 2021 , Edited by admin on Sat Jun 26 04:36:41 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
BINDER->LIGAND
BINDING
Related Record Type Details
METABOLITE ACTIVE -> PRODRUG
METABOLITE -> PARENT
METABOLITE -> PARENT
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC