Remifentanil

Identification

Name
Remifentanil
Accession Number
DB00899
Description

Remifentanil (marketed by Abbott as Ultiva) is a potent ultra short-acting synthetic opioid given to patients during surgery for pain relief and adjunctive to an anaesthetic. Remifentanil is a specific mu-type-opioid receptor agonist which means it reduces sympathetic nervous system tone, and causes respiratory depression and analgesia.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 376.4467
Monoisotopic: 376.199822016
Chemical Formula
C20H28N2O5
Synonyms
  • Remifentanil
  • Remifentanilo
  • Remifentanyl
External IDs
  • GI 87084X
  • IDS-NR-005

Pharmacology

Indication

For use during the induction and maintenance of general anesthesia.

Associated Therapies
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Remifentanil is an opioid agonist with rapid onset and peak effect and ultra-short duration of action. The opioid activity of remifentanil is antagonized by opioid antagonists such as naloxone. The analgesic effects of remifentanil are rapid in onset and offset. Its effects and side effects are dose dependent and similar to other opioids. Remifentanil in humans has a rapid blood-brain equilibration half-time of 1 ± 1 minutes (mean ± SD) and a rapid onset of action.

Mechanism of action

Remifentanil is a µ-opioid agonist with rapid onset and peak effect, and short duration of action. The µ-opioid activity of remifentanil is antagonized by opioid antagonists such as naloxone.

TargetActionsOrganism
AMu-type opioid receptor
agonist
Humans
UDelta-type opioid receptor
agonist
Humans
UKappa-type opioid receptor
agonist
Humans
Absorption
Not Available
Volume of distribution
  • 350 mL/kg
  • 452 ± 144 mL/kg [neonates]
  • 223 ± 30.6 mL/kg [adolescents]
Protein binding

70% (bound to plasma proteins)

Metabolism

By hydrolysis of the propanoic acid-methyl ester linkage by nonspecific blood and tissue esterases.

Route of elimination

Remifentanil is an esterase-metabolized opioid. The carboxylic acid metabolite is essentially inactive (1/4600 as potent as remifentanil in dogs) and is excreted by the kidneys with an elimination half-life of approximately 90 minutes.

Half-life

1-20 minutes

Clearance
  • 40 mL/min/kg [young, healthy adults]
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Remifentanil Action PathwayDrug action
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.
DrugInteraction
AcebutololRemifentanil may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of hypertension can be increased when Remifentanil is combined with Aceclofenac.
AcemetacinThe risk or severity of hypertension can be increased when Remifentanil is combined with Acemetacin.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Remifentanil.
AcetophenazineThe risk or severity of hypotension and CNS depression can be increased when Acetophenazine is combined with Remifentanil.
Acetylsalicylic acidThe risk or severity of hypertension can be increased when Remifentanil is combined with Acetylsalicylic acid.
AclidiniumThe risk or severity of adverse effects can be increased when Remifentanil is combined with Aclidinium.
AdenosineThe risk or severity of Tachycardia can be increased when Adenosine is combined with Remifentanil.
AgomelatineThe risk or severity of adverse effects can be increased when Remifentanil is combined with Agomelatine.
AlclofenacThe risk or severity of hypertension can be increased when Remifentanil is combined with Alclofenac.
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
  • Avoid alcohol. Ingesting alcohol may increase the sedative and CNS depressant effects of remifentanil.

Products

Product Ingredients
IngredientUNIICASInChI Key
Remifentanil hydrochloride5V444H5WIC132539-07-2WFBMIPUMYUHANP-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Remifentanil for InjectionPowder, for solutionIntravenousSandoz Canada IncorporatedNot applicableNot applicableCanada flag
Remifentanil for InjectionPowder, for solutionIntravenousTEVA Canada Limited2014-06-05Not applicableCanada flag
Remifentanil for InjectionPowder, for solutionIntravenousSandoz Canada IncorporatedNot applicableNot applicableCanada flag
Remifentanil for InjectionPowder, for solutionIntravenousTEVA Canada Limited2014-06-05Not applicableCanada flag
Remifentanil Hydrochloride for InjectionPowder, for solutionIntravenousSterimax IncNot applicableNot applicableCanada flag
Remifentanil Hydrochloride for InjectionPowder, for solutionIntravenousSterimax Inc2011-09-29Not applicableCanada flag
Remifentanil Hydrochloride for InjectionPowder, for solutionIntravenousSterimax Inc2011-09-27Not applicableCanada flag
UltivaInjection, powder, lyophilized, for solution1 mg/1mLIntravenousMylan Institutional LLC2020-04-15Not applicableUS flag
UltivaPowder, for solution1 mgIntravenousAbbvie1997-04-072013-10-02Canada flag
UltivaInjection, powder, lyophilized, for solution2 mg/2mLIntravenousAbbott1996-07-172012-11-29US flag
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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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Remifentanil HydrochlorideInjection, powder, lyophilized, for solution1 mg/1mLIntravenousFresenius Kabi USA, LLC2018-01-19Not applicableUS flag
Remifentanil HydrochlorideInjection, powder, lyophilized, for solution1 mg/1mLIntravenousFresenius Kabi USA, LLC2018-01-19Not applicableUS flag
Remifentanil HydrochlorideInjection, powder, lyophilized, for solution1 mg/1mLIntravenousFresenius Kabi USA, LLC2018-01-19Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
N01AH06 — Remifentanil
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acids and derivatives
Alternative Parents
Piperidinecarboxylic acids / Anilides / Dicarboxylic acids and derivatives / Tertiary carboxylic acid amides / Methyl esters / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
show 1 more
Substituents
Alpha-amino acid or derivatives / Amine / Anilide / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Carbonyl group / Carboxamide group / Carboxylic acid ester / Dicarboxylic acid or derivatives
show 15 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
monocarboxylic acid amide, alpha-amino acid ester, anilide, piperidinecarboxylate ester (CHEBI:8802)

Chemical Identifiers

UNII
P10582JYYK
CAS number
132875-61-7
InChI Key
ZTVQQQVZCWLTDF-UHFFFAOYSA-N
InChI
InChI=1S/C20H28N2O5/c1-4-17(23)22(16-8-6-5-7-9-16)20(19(25)27-3)11-14-21(15-12-20)13-10-18(24)26-2/h5-9H,4,10-15H2,1-3H3
IUPAC Name
methyl 1-(3-methoxy-3-oxopropyl)-4-(N-phenylpropanamido)piperidine-4-carboxylate
SMILES
CCC(=O)N(C1=CC=CC=C1)C1(CCN(CCC(=O)OC)CC1)C(=O)OC

References

Synthesis Reference

Jacob Mathew, J. Killgore, "New methods for the synthesis of alfentanil, sufentanil, and remifentanil." U.S. Patent US20060149071, issued July 06, 2006.

US20060149071
General References
Not Available
Human Metabolome Database
HMDB0015036
KEGG Drug
D08473
KEGG Compound
C08021
PubChem Compound
60815
PubChem Substance
46504538
ChemSpider
54803
BindingDB
50012491
RxNav
73032
ChEBI
8802
ChEMBL
CHEMBL1005
ZINC
ZINC000000538283
Therapeutic Targets Database
DAP000264
PharmGKB
PA451232
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Remifentanil
AHFS Codes
  • 28:08.08 — Opiate Agonists
FDA label
Download (380 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableAnaesthesia therapy1
4CompletedNot AvailableIntubation, Endotracheal1
4CompletedNot AvailablePatients Requiring Ambulatory Surgery Under General Anesthesia1
4CompletedBasic ScienceAnaesthesia therapy1
4CompletedBasic ScienceHealthy Volunteers1
4CompletedBasic SciencePharyngeal Dysfunction / Pharyngeal Swallowing1
4CompletedBasic ScienceSecondary Hyperalgesia1
4CompletedDiagnosticAlteration of Cognitive Function / Gastrointestinal Dysfunction1
4CompletedDiagnosticAnaesthesia therapy / Electroencephalography/ Drug Effect1
4CompletedDiagnosticAutonomic Nervous System Activity1

Pharmacoeconomics

Manufacturers
  • Bioniche teoranta
Packagers
  • Abbott Laboratories Ltd.
  • Bioniche Pharma
  • Hospira Inc.
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntravenous2 mg
Powder, for solutionIntravenous
Injection, solution, concentrate1 mg
Injection, solution, concentrate2 mg
Injection, solution, concentrate5 mg
Injection, powder, lyophilized, for solution1 mg
Injection, powder, lyophilized, for solution2 mg
Injection, powder, lyophilized, for solution5 mg
Injection, powder, lyophilized, for solutionIntravenous1 mg
Injection, powder, lyophilized, for solutionIntravenous2 mg
Injection, powder, for solution
Injection2 mg
Injection5 mg
Injection, powder, for solutionIntravenous; Parenteral1 mg
Injection, powder, for solutionIntravenous; Parenteral2 mg
Injection, powder, for solutionIntravenous; Parenteral5 mg
Injection, powder, lyophilized, for solutionIntravenous1 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous2 mg/2mL
Injection, powder, lyophilized, for solutionIntravenous5 mg/5mL
Powder, for solutionIntravenous1 mg
Powder, for solutionIntravenous2 mg
Powder, for solutionIntravenous5 mg
Injection1 mg
Injection, solutionIntravenous2 mg
Injection, solutionIntravenous5 mg
Injection
Prices
Unit descriptionCostUnit
Ultiva 5 mg vial118.15USD vial
Ultiva 2 mg vial57.2USD vial
Ultiva 1 mg vial30.19USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5019583No1991-05-282010-07-12US flag
US5866591Yes1999-02-022018-03-10US flag
Additional Data Available
  • Filed On
    Filed On

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

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP1.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.591 mg/mLALOGPS
logP1.75ALOGPS
logP1.52ChemAxon
logS-2.8ALOGPS
pKa (Strongest Basic)7.51ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area76.15 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity100.56 m3·mol-1ChemAxon
Polarizability40.82 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.6136
Blood Brain Barrier+0.9381
Caco-2 permeable-0.5271
P-glycoprotein substrateSubstrate0.7345
P-glycoprotein inhibitor IInhibitor0.8682
P-glycoprotein inhibitor IINon-inhibitor0.6428
Renal organic cation transporterNon-inhibitor0.7077
CYP450 2C9 substrateNon-substrate0.8041
CYP450 2D6 substrateNon-substrate0.8786
CYP450 3A4 substrateSubstrate0.6963
CYP450 1A2 substrateNon-inhibitor0.9355
CYP450 2C9 inhibitorNon-inhibitor0.8788
CYP450 2D6 inhibitorNon-inhibitor0.8838
CYP450 2C19 inhibitorNon-inhibitor0.8201
CYP450 3A4 inhibitorNon-inhibitor0.7827
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7945
Ames testNon AMES toxic0.7388
CarcinogenicityNon-carcinogens0.8554
BiodegradationNot ready biodegradable0.9428
Rat acute toxicity2.6994 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9589
hERG inhibition (predictor II)Inhibitor0.6126
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-004i-0009000000-b9035e2706d5ac9b57a7
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-02di-0397000000-c610a2d0adc44d55166b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03di-0930000000-436dbd271b442dcde5bf
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03e9-4900000000-79234a6e65fb22f3b487
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-01q9-9700000000-5ce11ade40e1a80e4958

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Voltage-gated calcium channel activity
Specific Function
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone...
Gene Name
OPRM1
Uniprot ID
P35372
Uniprot Name
Mu-type opioid receptor
Molecular Weight
44778.855 Da
References
  1. Scott LJ, Perry CM: Remifentanil: a review of its use during the induction and maintenance of general anaesthesia. Drugs. 2005;65(13):1793-823. [PubMed:16114980]
  2. Scott LJ, Perry CM: Spotlight on remifentanil for general anaesthesia. CNS Drugs. 2005;19(12):1069-74. [PubMed:16332149]
  3. Warner DS, Hindman BJ, Todd MM, Sawin PD, Kirchner J, Roland CL, Jamerson BD: Intracranial pressure and hemodynamic effects of remifentanil versus alfentanil in patients undergoing supratentorial craniotomy. Anesth Analg. 1996 Aug;83(2):348-53. [PubMed:8694317]
  4. Guy J, Hindman BJ, Baker KZ, Borel CO, Maktabi M, Ostapkovich N, Kirchner J, Todd MM, Fogarty-Mack P, Yancy V, Sokoll MD, McAllister A, Roland C, Young WL, Warner DS: Comparison of remifentanil and fentanyl in patients undergoing craniotomy for supratentorial space-occupying lesions. Anesthesiology. 1997 Mar;86(3):514-24. [PubMed:9066316]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  6. Hoke JF, Cunningham F, James MK, Muir KT, Hoffman WE: Comparative pharmacokinetics and pharmacodynamics of remifentanil, its principle metabolite (GR90291) and alfentanil in dogs. J Pharmacol Exp Ther. 1997 Apr;281(1):226-32. [PubMed:9103501]
  7. Patel SS, Spencer CM: Remifentanil. Drugs. 1996 Sep;52(3):417-27; discussion 428. [PubMed:8875131]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Opioid receptor activity
Specific Function
G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine n...
Gene Name
OPRD1
Uniprot ID
P41143
Uniprot Name
Delta-type opioid receptor
Molecular Weight
40368.235 Da
References
  1. Stucke AG, Zuperku EJ, Sanchez A, Tonkovic-Capin M, Tonkovic-Capin V, Mustapic S, Stuth EA: Opioid receptors on bulbospinal respiratory neurons are not activated during neuronal depression by clinically relevant opioid concentrations. J Neurophysiol. 2008 Nov;100(5):2878-88. doi: 10.1152/jn.90620.2008. Epub 2008 Sep 24. [PubMed:18815346]
  2. Rodrigues AR, Castro MS, Francischi JN, Perez AC, Duarte ID: Participation of ATP-sensitive K+ channels in the peripheral antinociceptive effect of fentanyl in rats. Braz J Med Biol Res. 2005 Jan;38(1):91-7. Epub 2005 Jan 18. [PubMed:15665994]
  3. Poonawala T, Levay-Young BK, Hebbel RP, Gupta K: Opioids heal ischemic wounds in the rat. Wound Repair Regen. 2005 Mar-Apr;13(2):165-74. [PubMed:15828941]
  4. Sahin AS, Duman A, Atalik EK, Ogun CO, Sahin TK, Erol A, Ozergin U: The mechanisms of the direct vascular effects of fentanyl on isolated human saphenous veins in vitro. J Cardiothorac Vasc Anesth. 2005 Apr;19(2):197-200. [PubMed:15868528]
  5. Darwish M, Tempero K, Kirby M, Thompson J: Pharmacokinetics and dose proportionality of fentanyl effervescent buccal tablets in healthy volunteers. Clin Pharmacokinet. 2005;44(12):1279-86. [PubMed:16372825]
  6. Darwish M, Kirby M, Robertson P Jr, Tracewell W, Jiang JG: Pharmacokinetic properties of fentanyl effervescent buccal tablets: a phase I, open-label, crossover study of single-dose 100, 200, 400, and 800 microg in healthy adult volunteers. Clin Ther. 2006 May;28(5):707-14. [PubMed:16861092]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Opioid receptor activity
Specific Function
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synt...
Gene Name
OPRK1
Uniprot ID
P41145
Uniprot Name
Kappa-type opioid receptor
Molecular Weight
42644.665 Da
References
  1. Wong GT, Li R, Jiang LL, Irwin MG: Remifentanil post-conditioning attenuates cardiac ischemia-reperfusion injury via kappa or delta opioid receptor activation. Acta Anaesthesiol Scand. 2010 Apr;54(4):510-8. doi: 10.1111/j.1399-6576.2009.02145.x. Epub 2009 Oct 29. [PubMed:19878098]
  2. Pascoe JE, Williams KL, Mukhopadhyay P, Rice KC, Woods JH, Ko MC: Effects of mu, kappa, and delta opioid receptor agonists on the function of hypothalamic-pituitary-adrenal axis in monkeys. Psychoneuroendocrinology. 2008 May;33(4):478-86. doi: 10.1016/j.psyneuen.2008.01.006. Epub 2008 Mar 5. [PubMed:18325678]

Drug created on June 13, 2005 07:24 / Updated on October 19, 2020 07:46

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