Delving into the Latest Updates on Alfentanil Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Alfentanil hydrochloride (USP), Alfentanil sublingual, Alfentanyl

+ [7]

Target

Opioid receptors

Mechanism

Opioid receptors agonists(Opioid receptors agonists)

Therapeutic Areas

Other Diseases

Active Indication

Anesthesia

Inactive Indication

Acute PainAnalgesia

Originator Organization

Akorn, Inc.

Active Organization

Rising Pharmaceuticals, Inc.Startup

Yichang Humanwell Pharmaceuticals Co., Ltd.

Inactive Organization

Jiangsu Nhwa Pharmaceutical Co., Ltd.

Orexo AB

Drug Highest PhaseApproved

First Approval Date

US (29 Dec 1986),

Anesthesia

RegulationOrphan Drug (US), Priority Review (CN)

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Structure/Sequence

Molecular FormulaC21H32N6O3

InChIKeyIDBPHNDTYPBSNI-UHFFFAOYSA-N

CAS Registry71195-58-9

View All Structures (2)

AbstractBackground and PurposeFentanyls and nitazenes are μ‐opioid receptor agonists responsible for a large number of opioid overdose deaths. Here, we determined the potency, dissociation kinetics and antagonism by naloxone at the μ receptor of several fentanyl and nitazene analogues, compared to morphine and DAMGO.Experimental ApproachIn vitro assays of G protein activation and signalling and arrestin recruitment were performed. AtT20 cells expressing μ receptors were loaded with a membrane potential dye and changes in fluorescence used to determine agonist potency, dissociation kinetics and susceptibility to antagonism by naloxone. BRET experiments were undertaken in HEK293T cells expressing μ receptors to assess Gi protein activation and β‐arrestin 2 recruitment.Key ResultsThe apparent rate of agonist dissociation from the μ receptor varied: morphine, DAMGO, alfentanil and fentanyl dissociated rapidly, whereas isotonitazene, etonitazene, ohmefentanyl and carfentanil dissociated slowly. Slowly dissociating agonists were more resistant to antagonism by naloxone. For carfentanil, the slow apparent rate of dissociation was not because of G protein receptor kinase‐mediated arrestin recruitment as its apparent rate of dissociation was not increased by inhibition of G protein‐coupled receptor kinases (GRKs) with Compound 101. The in vitro relative potencies of fentanyls and nitazenes compared to morphine were much lower than that previously observed in in vivo experiments.Conclusions and ImplicationsWith fentanyls and nitazenes that slowly dissociate from the μ receptor, antagonism by naloxone is pseudo‐competitive. In overdoses involving fentanyls and nitazenes, higher doses of naloxone may be required for reversal than those normally used to reverse heroin overdose.

01 Jan 2025·CPT: Pharmacometrics & Systems Pharmacology

PBPK modeling: What is the role of CYP3A4 expression in the gastrointestinal tract to accurately predict first‐pass metabolism?

Review

Author: Perrier, Jérémy ; Dallmann, André ; Frechen, Sebastian ; Henriot, Justine ; Dupuis, François

AbstractGastrointestinal first‐pass metabolism plays an important role in bioavailability and in drug–drug interactions. Physiologically‐based pharmacokinetic (PBPK) modeling is a powerful tool to integrate these processes mechanistically. However, a correct bottom‐up prediction of GI first‐pass metabolism is challenging and depends on various model parameters like the level of enzyme expression and the basolateral intestinal mucosa permeability (Pmucosa). This work aimed to investigate if cytochrome P450 (CYP) 3A4 expression could help predict the first‐pass effect using PBPK modeling or whether additional factors like Pmucosa do play additional roles using PBPK modeling. To this end, a systematic review of the absolute CYP3A expression in the human gastrointestinal tract and liver was conducted. The resulting CYP3A4 expression profile and two previously published profiles were applied to PBPK models of seven CYP3A4 substrates (alfentanil, alprazolam, felodipine, midazolam, sildenafil, triazolam, and verapamil) built‐in PK‐Sim®. For each compound, it was assessed whether first‐pass metabolism could be adequately predicted based on the integrated CYP3A4 expression profile alone or whether an optimization of Pmucosa was required. Evaluation criteria were the precision of the predicted interstudy bioavailabilities and area under the concentration–time curves. It was found that none of the expression profiles provided upfront an adequate description of the extent of GI metabolism and that optimization of Pmucosa as a compound‐specific parameter improved the prediction of most models. Our findings indicate that a pure bottom‐up prediction of gastrointestinal first‐pass metabolism is currently not possible and that compound‐specific features like Pmucosa must be considered as well.

01 Jan 2025·Pediatric Anesthesia

Evaluation of propofol‐based procedural sedation in pediatric hemato‐oncological patients provided by physician assistants in anesthesia

Article

Author: van Langeveld, I. ; Hampsink, B. ; Aalbers, T. ; Prudon, I. ; Dors, N. ; Malagon, I. ; Scheffer, G. J. ; Bronkhorst, E. M. ; Hendriks, M. ; Koning, R.

AbstractBackgroundProcedural sedation and analgesia are required for painful hemato‐oncological procedures such as lumbar and bone marrow punctures. At our institution, sedation with propofol and alfentanil is usually provided by Physician Assistants in Anesthesia. We evaluated the adverse events during the PSA program for children, provided by Physician Assistants in Anesthesia.Patients and MethodsWe included pediatric patients meeting our criteria for deep sedation by a Physician Assistants in Anesthesia, scheduled for a hemato‐oncological procedure at the Amalia Children's Hospital at the Radboudumc Nijmegen. The primary outcome was oxygen desaturation below 92% for more than 20 s. We prospectively collected data on demographics, current health problems, type of procedure, need for airway interventions, and hypotension.ResultsWe collected data from 437 sedation sessions involving 71 patients. No oxygen desaturation below 92% lasting longer than 20 s occurred. In 2 cases, a jaw thrust was performed. No invasive airway techniques (oropharyngeal cannula, laryngeal mask, or intubation) were required. A significant drop in mean arterial pressure was seen in 2 out of 437 cases (0.5%). There was no occurrence of cardiopulmonary resuscitation or other adverse events such as aspiration or laryngeal spasm.ConclusionsSedation and analgesia for short painful procedures in selected pediatric hemato‐oncological units with a dedicated protocol may be safely provided by trained and certified Physician Assistants in Anesthesia.

100 Deals associated with Alfentanil Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D00835	Alfentanil Hydrochloride	N01AH02	DB00802

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Anesthesia	US	Rising Pharmaceuticals, Inc.Startup	29 Dec 1986

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Analgesia	Discovery	CN	Jiangsu Nhwa Pharmaceutical Co., Ltd.	06 Jun 2018
Anesthesia	Discovery	CN	Jiangsu Nhwa Pharmaceutical Co., Ltd.	06 Jun 2018
Acute Pain	Discovery	CZ	Orexo AB	08 Oct 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ChiCTR2200062034 (Pubmed \| BMC Anesthesiol)	Phase 1	-	96	Alfentanil 20 µg/kg	ztotozvgyj(vqinfahtlj) = zlyifihvuf cppetifdrv (yiemwrzcgl ) View more	Positive	13 Aug 2024
				Alfentanil 25 µg/kg	(ntytqamhpd) = fzsyguqnug vxnpcoqjtb (pwmjdfwljo )
NCT03359395 (CTgov)	Phase 4	-	100	Alfentanil (Alfentanil)	byawcogdhr(xbuibuogqp) = cuyhyjzagn thxgzmmnga (ebdslviqzg, zdwpkvuora - equykocdwz) View more	-	08 Jul 2021
				Placebos (Placebo)	byawcogdhr(xbuibuogqp) = rbplfjpvdq thxgzmmnga (ebdslviqzg, nevmucvxhs - piiklnddbb) View more
NCT01008059 (CTgov)	Not Applicable	-	6	Alfentanil	oygtizzacb(gjqcclxjox) = kvvnsmutpd blrbaabolh (ibtbgyaggx, zxiizoqnwu - itinftqhkn) View more	-	17 May 2019
NCT01094574 (CTgov)	Not Applicable	Pain \| Inflammation	10	Alfentanil (Alfentanil)	vattygmgzm(wmxvmigndi) = izmauabwum wbdwozwktd (gfkxkiczua, dkudqepomk - luelaacwxs) View more	-	24 Feb 2017
				Propranolol (Propranolol)	vattygmgzm(wmxvmigndi) = nfmkhgcduc wbdwozwktd (gfkxkiczua, gvmardoalt - jrlffdskrz) View more
NCT00997126 (CTgov)	Phase 4	Sedation	126	Propofol (Propofol)	lattyjyyff(qgkbyxmbik) = lwmtlpqeud znhixholue (xdcpbwwztm, ivhcjwkzzy - zfxzwnmaqz) View more	-	27 Jan 2017
				Alfentanil (Alfentanil)	lattyjyyff(qgkbyxmbik) = ieotemscfz znhixholue (xdcpbwwztm, azdwinkmke - pcxlbpncmv) View more
NCT00672438 (CTgov)	Not Applicable	Pain	242	Alfentanil	rbaxwsbucp(bcysiuvlly) = lnefbvbddu yvjfwleecv (tkbwxnkjbe, ajuobxfbuw - lnloyjlhat) View more	-	21 Jul 2016
NCT01470170 (CTgov)	Phase 4	Hypoxia	173	Targeted controlled infusion+Propofol+normal saline+Alfentanil (Group1)	ocywfzbdfk(tpietjepgf) = otjoiiyojp nvdnfhsoaf (qxnmqawrga, dswcrvrfuv - yaxqectoja) View more	-	13 Aug 2015
				Targeted controlled infusion+Propofol+normal saline+Alfentanil (Group 3)	ocywfzbdfk(tpietjepgf) = yzhqfiqqwe nvdnfhsoaf (qxnmqawrga, ookzkjdvlv - yagedgopon) View more
NCT00997113 (CTgov)	Phase 4	Sedation	20	propofol (Propofol)	vfykwgnlwq(ralhzbfhri) = ypysxcsahi fordmpkpky (zeokdcgfqs, btjgpeahtv - qcnscjikmt) View more	-	25 Sep 2014
				propofol+alfentanil (Propofol/Alfentanil)	vfykwgnlwq(ralhzbfhri) = xxxbegolok fordmpkpky (zeokdcgfqs, ozbdefksrn - dfbwgmuial) View more
NCT00538850 (CTgov)	Phase 3	Cancer Pain \| Neoplasms	130	Placebo+Fentanyl sublingual spray	uarayiforn(weaofofyxm) = igbohjautc cydobluwbu (kcyvxxxzvg, fviceyxwaw - gelxskzwdd) View more	-	05 Mar 2014
Pubmed \| Clin J Pain	Not Applicable	Pain	-	Alfentanil 15 mcg/kg	uvtybxpujf(xprkzgkoyc) = piwbescwph xvxlpymttm (mzazmbluhp, ±26.5)	-	01 Jan 2014