Identification

Name
Sufentanil
Accession Number
DB00708  (APRD00671, DB05563)
Type
Small Molecule
Groups
Approved, Investigational
Description

Sufentanil is an opioid analgesic that is used as an adjunct in anesthesia, in balanced anesthesia, and as a primary anesthetic agent. It is administered by the intravenous, epidural and sublingual routes.

Also known as Dsuvia, the sublingual form is used for the management of acute pain in adults that is severe to warrant the use of an opioid analgesic in certified medically supervised healthcare settings, including hospitals, surgical centers, and emergency departments [10]. Consideration may be made in the future for the use of the sublingual form in the US military in cases where analgesia is required immediately [11].

The sublingual form, manufactured by AcelRx Pharmaceuticals, Inc. (AcelRx), was approved on November 2, 2018 [10]. This route of administration is intended to be a simple, effective, non-invasive analgesic option to enable healthcare professionals to rapidly manage acute pain without difficult intravenous or epidural administration [10], [4].

Structure
Thumb
Synonyms
  • N-(4-(Methoxymethyl)-1-(2-(2-thienyl)ethyl)-4-piperidinyl)-N-phenylpropanamide
  • N-(4-(Methoxymethyl)-1-(2-(2-thienyl)ethyl)-4-piperidyl)propionanilide
  • Sufentanil
  • Sufentanilo
  • Sufentanilum
  • Sufentanyl
External IDs
IDS-NS-001 / R 30,730 / R 30730 / R 33800 / R-30730
Product Ingredients
IngredientUNIICASInChI Key
Sufentanil citrateS9ZFX8403R60561-17-3OJCZPLDERGDQRJ-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DsuviaTablet30 ug/1SublingualAcelRx Pharmaceuticals, Inc2018-11-02Not applicableUs
SufentaSolution50 ug/1mLIntravenousTaylor Pharmaceuticals2008-07-02Not applicableUs
Sufenta Inj 50mcg/mlLiquid50 mcgIntravenousJanssen Pharmaceutica, Division Of Janssen Ortho Inc.1985-12-311996-09-10Canada
Sufenta Inj 50mcg/mlLiquid50 mcgEpidural; IntravenousJanssen Pharmaceuticals1985-12-312007-11-26Canada
Sufentanil CitrateInjection50 ug/1mLEpidural; IntravenousAkorn2010-12-01Not applicableUs
Sufentanil CitrateInjection, solution50 ug/1mLEpidural; IntravenousHospira, Inc.2006-10-062006-10-06Us
Sufentanil Citrate Injection USPSolution50 mcgEpidural; IntravenousSandoz Canada Incorporated2001-08-01Not applicableCanada
Sufentanil Citrate Injection, USPSolution50 mcgEpidural; IntravenousSterimax Inc2016-10-18Not applicableCanada
ZalvisoTablet15 μgSublingualGrunenthal Gmb H2015-09-18Not applicableEu
ZalvisoTablet15 μgSublingualGrunenthal Gmb H2015-09-18Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Sufentanil CitrateInjection0.05 mg/1mLEpidural; IntravenousWest-Ward Pharmaceuticals Corp.1995-12-15Not applicableUs
Sufentanil CitrateInjection0.05 mg/1mLEpidural; IntravenousBaxter Laboratories2002-12-022014-03-31Us
Sufentanil CitrateInjection0.05 mg/1mLEpidural; IntravenousWest-Ward Pharmaceuticals Corp.1995-12-15Not applicableUs
Sufentanil CitrateInjection0.05 mg/1mLEpidural; IntravenousWest-Ward Pharmaceuticals Corp.1995-12-15Not applicableUs
Sufentanil CitrateInjection, solution50 ug/1mLEpidural; IntravenousHospira, Inc.2005-07-26Not applicableUs
International/Other Brands
Chronogesic (DURECT) / Disufen (Angenerico) / Fastfen (Cristália) / Sufenta (Janssen) / Sufenta Forte (Janssen) / Sufenta mite (Janssen) / Sufentil (Claris Lifesciences Ltd.) / Zuftil (Pisa)
Categories
UNII
AFE2YW0IIZ
CAS number
56030-54-7
Weight
Average: 386.551
Monoisotopic: 386.202798904
Chemical Formula
C22H30N2O2S
InChI Key
GGCSSNBKKAUURC-UHFFFAOYSA-N
InChI
InChI=1S/C22H30N2O2S/c1-3-21(25)24(19-8-5-4-6-9-19)22(18-26-2)12-15-23(16-13-22)14-11-20-10-7-17-27-20/h4-10,17H,3,11-16,18H2,1-2H3
IUPAC Name
N-[4-(methoxymethyl)-1-[2-(thiophen-2-yl)ethyl]piperidin-4-yl]-N-phenylpropanamide
SMILES
CCC(=O)N(C1=CC=CC=C1)C1(COC)CCN(CCC2=CC=CS2)CC1

Pharmacology

Indication

The indications for this drug are as follows:

  1. As an analgesic adjunct in the maintenance of balanced general anesthesia in patients who are intubated and ventilated.

  2. As a primary anesthetic agent for the induction and maintenance of anesthesia with 100% oxygen in patients undergoing major surgical procedures, in patients who are intubated and ventilated, such as cardiovascular surgery or neurosurgical procedures in the sitting position, to provide favorable myocardial and cerebral oxygen balance or when extended postoperative ventilation is anticipated.

  3. For epidural administration as an analgesic combined with low dose (usually 12.5 mg per administration) bupivacaine usually during labor and vaginal delivery

  4. The sublingual form is indicated for the management of acute pain in adults that is severe to warrant the use of an opioid analgesic in certified medically supervised healthcare settings, including hospitals, surgical centers, and emergency departments.

[Label]

Associated Conditions
Associated Therapies
Pharmacodynamics

Effect on the Central Nervous System (CNS)

In clinical settings, sufentanil exerts its principal pharmacologic effects on the central nervous system. Its primary therapeutic actions are analgesia and sedation. Sufentanil may increase pain tolerance and decrease the perception of pain. This drug depresses the respiratory centers, depresses the cough reflex, and constricts the pupils [12], [9]. When used in balanced general anesthesia, sufentanil has been reported to be as much as 10 times as potent as fentanyl. When administered intravenously as a primary anesthetic agent with 100% oxygen, sufentanil is approximately 5 to 7 times as potent as fentanyl [Label]. High doses of intravenous sufentanil have been shown to cause muscle rigidity, likely as a result of an effect on the substantia nigra and the striate nucleus in the brain. Sleep-inducing (hypnotic) activity can be demonstrated by EEG alterations [Label].

Effects on the Respiratory System

Sufentanil may cause respiratory depression [Label].

Effects on the Cardiovascular System

Sufentanil causes peripheral vasodilation which may result in orthostatic hypotension or syncope. Bradycardia may also occur [12]. Clinical signs or symptoms of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes and sweating and/or orthostatic hypotension [Label].

Effects on the Gastrointestinal Tract

Sufentanil causes a reduction in motility associated with an increase in smooth muscle tone in both the antrum of the stomach and duodenum. Digestion of food in the small intestine may be delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased and lead to spasm, resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of the sphincter of Oddi, as well as temporary elevations in serum amylase [Label].

Mechanism of action

Sufentanil is a synthetic, potent opioid with highly selective binding to μ-opioid receptors [12]. These receptors are widely distributed in the human brain, spinal cord, and other tissues [8], [9].

In general, opioids decrease cAMP (affecting neural signaling pathways), decrease neurotransmitter release, and cause membrane hyperpolarization, all of which contribute to the relief of painful symptoms [9].

Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic neural transmission via G-proteins that activate effector proteins. Binding of the opiate receptor leads to the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP, located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. The release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine, and noradrenaline is then inhibited [9].

Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist), also preventing neurotransmitter release [9].

Sufentanil and other opioids open calcium-dependent inwardly rectifying potassium channels, resulting in hyperpolarization and reduced neuronal excitability [8], [9].

TargetActionsOrganism
AMu-type opioid receptor
agonist
Human
UDelta-type opioid receptor
agonist
Human
UKappa-type opioid receptorNot AvailableHuman
Absorption

Bioavailability of a single sublingual tablet was 52%, decreasing to 35% with repeat dosing [5].

After epidural administration of incremental doses totaling 5 to 40 mcg sufentanil during labor and delivery, maternal and neonatal sufentanil plasma concentrations were at or near the 0.05 to 0.1 ng/mL limit of detection, and were slightly higher in mothers than in their infants [Label].

Volume of distribution

Sufentanil has a distribution time of 1.4 minutes and redistribution time of 17.1 minutes [Label]. The central volume of distribution after intravenous application of sufentanil is approximately 14 L and the volume of distribution at steady state is approximately 350 L [12].

Protein binding

Plasma protein binding of sufentanil, related to the alpha acid glycoprotein concentration, was approximately 93% in healthy males, 91% in mothers and 79% in neonates [Label].

Metabolism

The liver and small intestine are the major sites of biotransformation [Label]. Sufentanil is rapidly metabolized to a number of inactive metabolites, with oxidative N- and O-dealkylation being the major routes of elimination [12].

Route of elimination

Approximately 80% of the administered dose is excreted within 24 hours and only 2% of the dose is eliminated as unchanged drug [Label].

Half life

The elimination half-life is 164 minutes in adults when administered intravenously (IV). The elimination half-life of sufentanil is shorter (e.g. 97 +/- 42 minutes) in infants and children, and longer in neonates (e.g. 434 +/- 160 minutes) compared to that of adolescents and adults [Label].

After a single administration of a 15 microgram sufentanil sublingual tablet, mean terminal phase half-lives in the range of 6-10 hours have been observed. After multiple administrations, a longer average terminal half-life of up to 18 hours was measured, owing to the higher plasma concentrations of sufentanil achieved after repeated dosing and due to the possibility to quantify these concentrations over a longer time period [12].

Clearance

The total plasma clearance after single intravenous administration is about 917 l/min [12].

The clearance of sufentanil in healthy neonates is approximately one-half that in adults and children. The clearance rate of sufentanil can be further reduced by up to a third in neonates with cardiovascular disease [Label].

Toxicity

LD50: 18.7 mg/kg (IV in mice) [MSDS]

A Note on Respiratory Depression

Major, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even in cases where it is used as recommended. Respiratory depression may lead to respiratory arrest and death if not diagnosed and treated appropriately. This drug should be administered only by persons specifically trained in the use of anesthetic drugs and the management of the respiratory effects of potent opioids, including respiration and cardiac resuscitation of patients in the age group being treated. This training must include the establishment and maintenance of a patent airway and assisted ventilation [Label].

Carcinogenesis Long-term studies in animals to evaluate the carcinogenic potential of sufentanil have not been conducted [Label].

Mutagenesis Sufentanil was not found to be genotoxic in the in vitro bacterial reverse mutation assay (Ames assay) or in the in vivo rat bone marrow micronucleous assay [Label].

Reproductive Toxicity

Sufentanil caused embryolethality in rats and rabbits treated for 10-30 days during pregnancy with 2.5 times the maximum human dose by intravenous administration. The embryolethal effect was thought to be secondary to the toxicity for the mother animal model. No negative effects were noted in another study in rats that were treated with 20 times the maximum human dose in the period of organogenesis. The preclinical effects were only seen following administrations of levels significantly above the maximum human dose, which is therefore of minimal relevance for clinical use [12].

Pregnancy

May cause fetal harm [Label]

The Use in Lactation

Infants exposed to this drug through breast milk should be monitored for excess sedation and respiratory depression [Label].

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Sufentanil Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Sufentanil.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Sufentanil.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Sufentanil is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Sufentanil is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when Sufentanil is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Sufentanil.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when Sufentanil is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Sufentanil.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Sufentanil is combined with 4-Methoxyamphetamine.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Sufentanil.
Food Interactions
Not Available

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
  1. Authors unspecified: Drug and Device News. P T. 2017 Dec;42(12):726-763. [PubMed:29234209]
  2. Miner JR, Rafique Z, Minkowitz HS, DiDonato KP, Palmer PP: Sufentanil sublingual tablet 30mcg for moderate-to-severe acute pain in the ED. Am J Emerg Med. 2018 Jun;36(6):954-961. doi: 10.1016/j.ajem.2017.10.058. Epub 2017 Oct 31. [PubMed:29122372]
  3. Willsie SK, Evashenk MA, Hamel LG, Hwang SS, Chiang YK, Palmer PP: Pharmacokinetic properties of single- and repeated-dose sufentanil sublingual tablets in healthy volunteers. Clin Ther. 2015 Jan 1;37(1):145-55. doi: 10.1016/j.clinthera.2014.11.001. Epub 2014 Dec 24. [PubMed:25544247]
  4. Ringold FG, Minkowitz HS, Gan TJ, Aqua KA, Chiang YK, Evashenk MA, Palmer PP: Sufentanil sublingual tablet system for the management of postoperative pain following open abdominal surgery: a randomized, placebo-controlled study. Reg Anesth Pain Med. 2015 Jan-Feb;40(1):22-30. doi: 10.1097/AAP.0000000000000152. [PubMed:25318408]
  5. Fisher DM, Chang P, Wada DR, Dahan A, Palmer PP: Pharmacokinetic Properties of a Sufentanil Sublingual Tablet Intended to Treat Acute Pain. Anesthesiology. 2018 May;128(5):943-952. doi: 10.1097/ALN.0000000000002145. [PubMed:29498947]
  6. Vardanyan RS, Hruby VJ: Fentanyl-related compounds and derivatives: current status and future prospects for pharmaceutical applications. Future Med Chem. 2014 Mar;6(4):385-412. doi: 10.4155/fmc.13.215. [PubMed:24635521]
  7. Pergolizzi JV Jr, LeQuang JA, Berger GK, Raffa RB: The Basic Pharmacology of Opioids Informs the Opioid Discourse about Misuse and Abuse: A Review. Pain Ther. 2017 Jun;6(1):1-16. doi: 10.1007/s40122-017-0068-3. Epub 2017 Mar 24. [PubMed:28341939]
  8. Sobczak M, Salaga M, Storr MA, Fichna J: Physiology, signaling, and pharmacology of opioid receptors and their ligands in the gastrointestinal tract: current concepts and future perspectives. J Gastroenterol. 2014 Jan;49(1):24-45. doi: 10.1007/s00535-013-0753-x. Epub 2013 Feb 9. [PubMed:23397116]
  9. Pathan H, Williams J: Basic opioid pharmacology: an update. Br J Pain. 2012 Feb;6(1):11-6. doi: 10.1177/2049463712438493. [PubMed:26516461]
  10. FDA approves Dsuvia [Link]
  11. Noting Military Potential, FDA Approves Powerful Painkiller Dsuvia [Link]
  12. Sufentanil EMA label [File]
  13. Sufentanil [File]
External Links
Human Metabolome Database
HMDB0014846
KEGG Drug
D05938
KEGG Compound
C08022
PubChem Compound
41693
PubChem Substance
46504737
ChemSpider
38043
BindingDB
94503
ChEBI
9316
ChEMBL
CHEMBL658
Therapeutic Targets Database
DAP000357
PharmGKB
PA451527
IUPHAR
3534
Guide to Pharmacology
GtP Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Sufentanil
ATC Codes
N01AH03 — Sufentanil
AHFS Codes
  • 28:08.08 — Opiate Agonists
FDA label
Download (176 KB)
MSDS
Download (47.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic SciencePlasma Concentrations1
1, 2TerminatedTreatmentOpioids / Pain NOS1
2CompletedTreatmentAnaesthesia therapy1
2CompletedTreatmentMajor Upper or Lower Abdominal Surgery1
2CompletedTreatmentPain NOS1
2CompletedTreatmentPregnant Women1
2Not Yet RecruitingTreatmentHead Trauma1
2RecruitingTreatmentPrenatal Diagnosis1
2WithdrawnTreatmentPain, Chronic1
2, 3Active Not RecruitingTreatmentCerebral Hypoperfusion / Intubation, Endotracheal / Premedication1
2, 3Active Not RecruitingTreatmentIntubation, Endotracheal / Premedication1
2, 3Active Not RecruitingTreatmentMyocardial Injury1
2, 3CompletedSupportive CareHealthy Volunteers / Pelvic Floor Disorders / Prolonged Labour1
3CompletedPreventionNormal Pregnancies1
3CompletedTreatmentChild Comfort / Intensive Care Units / Morphine / Pediatric1
3CompletedTreatmentModerate-to-severe Acute Pain1
3CompletedTreatmentPain, Acute1
3CompletedTreatmentPost Operative Pain1
3CompletedTreatmentPost-Operative Pain3
3CompletedTreatmentPostoperative pain1
3Not Yet RecruitingTreatmentOther Complications of Obstetric Anesthesia - Delivered / Pain, Obstetric1
3RecruitingTreatmentLumbar epidural anesthesia therapy1
4Active Not RecruitingTreatmentDriving Performance After Minor Ambulatory Surgery / Minor Surgical Procedures With Monitored Anesthesia Care1
4Active Not RecruitingTreatmentTrigeminal Neuralgia (TN)1
4CompletedNot AvailableAortic Aneurysms1
4CompletedBasic ScienceAnaesthesia therapy1
4CompletedPreventionAortic Valve Stenosis / Ischaemic Heart Diseases1
4CompletedSupportive CarePain NOS1
4CompletedSupportive CarePost-Operative Nausea and Vomiting (PONV) / Postoperative pain1
4CompletedTreatmentAnalgesics / Pain, Chronic / Postoperative pain1
4CompletedTreatmentNumeric Pain Rating Scale > 5 / 10 / Severe Traumatic Pain1
4CompletedTreatmentPain NOS3
4CompletedTreatmentPostoperative pain2
4CompletedTreatmentSingle Traumatic Limb Injury With Severe Pain (Score > 5/10 on Numerical Pain Scale)1
4Enrolling by InvitationSupportive CarePostoperative; Dysfunction Following Cardiac Surgery1
4Not Yet RecruitingPreventionPostoperative Cognitive Dysfunction / Postoperative Delirium1
4Not Yet RecruitingTreatmentAnalgesia, Patient-Controlled1
4Not Yet RecruitingTreatmentAnesthesia; Functional1
4Not Yet RecruitingTreatmentOpioids Use / Postoperative pain1
4RecruitingPreventionCoronary Artery Bypass Graft Redo / General Anesthetic Drug Adverse Reaction1
4RecruitingSupportive CarePregnancy1
4RecruitingTreatmentAnalgesia, Patient-Controlled / Anesthesia; Spinal / Epidural Analgesia / Intravenous Drug Delivery Systems / Morphine / Surgery, Colorectal1
4RecruitingTreatmentArteriovenous Malformations1
4RecruitingTreatmentLabour Pain1
4RecruitingTreatmentLabour Pain / Lumbar epidural anesthesia therapy / Opioids1
4RecruitingTreatmentPain, Acute1
4RecruitingTreatmentPatients Ongoing Elective Abdominal Laparoscopy1
4RecruitingTreatmentPostoperative pain1
4TerminatedTreatmentAnalgesia / Sedation therapy1
4TerminatedTreatmentThoracic Surgery1
4Unknown StatusTreatmentAdrenal Suppression / Hemodynamics Instability1
4Unknown StatusTreatmentAnalgesia, Patient-Controlled / Arthroplasty / Gastric Resection1
Not AvailableCompletedNot AvailableAdequate Anesthesia With Unimpaired Motor Strength1
Not AvailableCompletedDiagnosticProstate Cancer1
Not AvailableCompletedOtherLoss of Consciousness1
Not AvailableCompletedPreventionAnaesthesia therapy / Pain NOS1
Not AvailableCompletedPreventionKidney Donation/Transplantation1
Not AvailableCompletedPreventionPost-Operative Nausea and Vomiting (PONV)1
Not AvailableCompletedScreeningKnee Surgery With Tourniquet1
Not AvailableCompletedSupportive CareEpidural Analgesia / Instrumental Delivery / Maternal Outcome / Neonatal Outcome1
Not AvailableCompletedSupportive CareEpidural Block / Malignant Neoplasm of Esophagus / Oesophagectomy1
Not AvailableCompletedSupportive CareTotal Knee Arthroplasty (TKA)1
Not AvailableCompletedTreatmentAnaesthesia therapy1
Not AvailableCompletedTreatmentAnesthesia Complications1
Not AvailableCompletedTreatmentBalanced Anesthesia1
Not AvailableCompletedTreatmentIschaemic Heart Diseases1
Not AvailableCompletedTreatmentLabour Pain1
Not AvailableCompletedTreatmentNeoplasms, Pancreatic1
Not AvailableCompletedTreatmentPediatric Ventricular Septal Defects1
Not AvailableCompletedTreatmentPost Operative Pain Management1
Not AvailableNot Yet RecruitingSupportive CareCardiovascular Disease (CVD)1
Not AvailableNot Yet RecruitingTreatmentAdult Disease / Liver Diseases1
Not AvailableNot Yet RecruitingTreatmentC.Delivery; Surgery (Previous), Gynecological1
Not AvailableNot Yet RecruitingTreatmentGeneral Surgery / Hallux Valgus1
Not AvailableNot Yet RecruitingTreatmentLiver Diseases / Neoplasms, Hepatic / Secondary Malignant Neoplasm of Liver1
Not AvailableRecruitingNot AvailableAnalgesic Quality / Mobility1
Not AvailableRecruitingOtherBronchoscopy1
Not AvailableRecruitingTreatmentLabour Analgesia1
Not AvailableRecruitingTreatmentLabour Pain1
Not AvailableRecruitingTreatmentPostoperative Complications1
Not AvailableTerminatedDiagnosticLabour Pain1
Not AvailableUnknown StatusHealth Services ResearchPregnancy1
Not AvailableUnknown StatusSupportive CareAdjunct to general anesthesia therapy1
Not AvailableUnknown StatusTreatmentHaemodynamic Fluctuations During Off-pump CABG1

Pharmacoeconomics

Manufacturers
  • Akorn inc
  • Baxter healthcare corp anesthesia and critical care
  • Hospira inc
  • Watson laboratories inc
Packagers
  • Akorn Inc.
  • Baxter International Inc.
  • Generamedix Inc.
  • Hospira Inc.
  • Mallinckrodt Inc.
  • Taylor Pharmaceuticals
Dosage forms
FormRouteStrength
TabletSublingual30 ug/1
SolutionIntravenous50 ug/1mL
LiquidEpidural; Intravenous50 mcg
LiquidIntravenous50 mcg
InjectionEpidural; Intravenous0.05 mg/1mL
InjectionEpidural; Intravenous50 ug/1mL
Injection, solutionEpidural; Intravenous50 ug/1mL
SolutionEpidural; Intravenous50 mcg
TabletSublingual15 μg
Prices
Unit descriptionCostUnit
Sufentanil citrate powder18927.0USD g
Sufenta 50 mcg/ml ampul5.38USD ml
Sufentanil 50 mcg/ml ampul3.92USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)136.3MSDS
water solubilitySolubleMSDS
logP3.95https://pubchem.ncbi.nlm.nih.gov/compound/sufentanil#section=Solubility
logS-3.71https://pubchem.ncbi.nlm.nih.gov/compound/sufentanil#section=Solubility
Predicted Properties
PropertyValueSource
Water Solubility0.012 mg/mLALOGPS
logP3.4ALOGPS
logP3.61ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)8.86ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area32.78 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity111.42 m3·mol-1ChemAxon
Polarizability43.85 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9875
Blood Brain Barrier+0.9886
Caco-2 permeable+0.5201
P-glycoprotein substrateSubstrate0.6673
P-glycoprotein inhibitor IInhibitor0.8275
P-glycoprotein inhibitor IIInhibitor0.8387
Renal organic cation transporterNon-inhibitor0.5594
CYP450 2C9 substrateNon-substrate0.7923
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.713
CYP450 1A2 substrateNon-inhibitor0.8954
CYP450 2C9 inhibitorNon-inhibitor0.7839
CYP450 2D6 inhibitorNon-inhibitor0.8416
CYP450 2C19 inhibitorNon-inhibitor0.5438
CYP450 3A4 inhibitorInhibitor0.6293
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6401
Ames testNon AMES toxic0.7695
CarcinogenicityNon-carcinogens0.8861
BiodegradationNot ready biodegradable0.9724
Rat acute toxicity3.0968 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9793
hERG inhibition (predictor II)Inhibitor0.772
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/MSsplash10-000i-0009000000-0f9e477eb2153eb20409
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000i-0096000000-73641c83c08b872641cd
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-06ri-1981000000-b5f4aaab095cc6fc533c
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03di-1900000000-2fdfd1d5fa6e43fa1604
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03di-4900000000-bd92c052347dc0822a01

Taxonomy

Description
This compound belongs to the class of organic compounds known as anilides. These are organic heterocyclic compounds derived from oxoacids RkE(=O)l(OH)m (l not 0) by replacing an OH group by the NHPh group or derivative formed by ring substitution.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Anilides
Alternative Parents
Aralkylamines / Piperidines / Thiophenes / Tertiary carboxylic acid amides / Heteroaromatic compounds / Trialkylamines / Amino acids and derivatives / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds
show 3 more
Substituents
Anilide / Aralkylamine / Piperidine / Tertiary carboxylic acid amide / Heteroaromatic compound / Thiophene / Amino acid or derivatives / Carboxamide group / Tertiary amine / Tertiary aliphatic amine
show 15 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
piperidines, thiophenes, ether, anilide (CHEBI:9316)

Targets

Kind
Protein
Organism
Human
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. Hurle MA: Changes in the expression of G protein-coupled receptor kinases and beta-arrestin 2 in rat brain during opioid tolerance and supersensitivity. J Neurochem. 2001 Apr;77(2):486-92. [PubMed:11299311]
  2. Levron JC: [Pharmacokinetics and pharmacodynamics of morphinomimetics in the central nervous system]. Agressologie. 1991;32(6-7):318-20. [PubMed:1688220]
  3. Ilien B, Galzi JL, Mejean A, Goeldner M, Hirth C: A mu-opioid receptor-filter assay. Rapid estimation of binding affinity of ligands and reversibility of long-lasting ligand-receptor complexes. Biochem Pharmacol. 1988 Oct 15;37(20):3843-51. [PubMed:2847746]
  4. Colpaert FC, Leysen JE, Michiels M, van den Hoogen RH: Epidural and intravenous sufentanil in the rat: analgesia, opiate receptor binding, and drug concentrations in plasma and brain. Anesthesiology. 1986 Jul;65(1):41-9. [PubMed:3014923]
  5. Leysen JE, Gommeren W: In vitro binding properties of 3H-sufentanil, a superior ligand for the mu-opiate receptor. Arch Int Pharmacodyn Ther. 1982 Dec;260(2):287-9. [PubMed:6131653]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
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. Freye E, Latasch L, Portoghese PS: The delta receptor is involved in sufentanil-induced respiratory depression--opioid subreceptors mediate different effects. Eur J Anaesthesiol. 1992 Nov;9(6):457-62. [PubMed:1330549]
  2. Zhu J, Xue JC, Law PY, Claude PA, Luo LY, Yin J, Chen C, Liu-Chen LY: The region in the mu opioid receptor conferring selectivity for sufentanil over the delta receptor is different from that over the kappa receptor. FEBS Lett. 1996 Apr 15;384(2):198-202. [PubMed:8612823]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Zhu J, Xue JC, Law PY, Claude PA, Luo LY, Yin J, Chen C, Liu-Chen LY: The region in the mu opioid receptor conferring selectivity for sufentanil over the delta receptor is different from that over the kappa receptor. FEBS Lett. 1996 Apr 15;384(2):198-202. [PubMed:8612823]
  2. Chang HM, Berde CB, Holz GG 4th, Steward GF, Kream RM: Sufentanil, morphine, met-enkephalin, and kappa-agonist (U-50,488H) inhibit substance P release from primary sensory neurons: a model for presynaptic spinal opioid actions. Anesthesiology. 1989 Apr;70(4):672-7. [PubMed:2467589]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Fisher DM, Chang P, Wada DR, Dahan A, Palmer PP: Pharmacokinetic Properties of a Sufentanil Sublingual Tablet Intended to Treat Acute Pain. Anesthesiology. 2018 May;128(5):943-952. doi: 10.1097/ALN.0000000000002145. [PubMed:29498947]
  2. Sufentanil EMA label [File]

Drug created on June 13, 2005 07:24 / Updated on November 20, 2018 00:45