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

Action

agonists

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

United States (29 Dec 1986),

Anesthesia

RegulationOrphan Drug (United States), Priority Review (China)

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Structure/Sequence

Molecular FormulaC21H35ClN6O4

InChIKeyYYESXRRYBUERKF-UHFFFAOYSA-N

CAS Registry70879-28-6

Pain is a common symptom in prehospital emergency care and pain treatment in this context can be challenging. While previous research has assessed the use of morphine and other synthetic opioids for pain management in this setting, the evaluation of alfentanil is limited. The objective of this study was to evaluate the safety and effect of intravenous alfentanil when administered by ambulance nurses in prehospital emergency care.

METHODS:

This retrospective observational study consecutively included patients suffering from pain, treated with alfentanil in a Swedish EMS service from September 2011 to 31 September 2022. Data regarding occurrence of adverse events (AE), serious adverse events (SAE) - were used for safety evaluation and pain scores with a visual analogue scale (VAS) before and after treatment were used for evaluation of pain treatment. These data were extracted from the electronic patients' medical records database for analysis. Univariate logistic regression analysis was used to identify significant predictors of AE following injection of alfentanil by nurses in prehospital emergency care.

RESULTS:

During the evaluation period 17,796 patients received pain relief with alfentanil. Adverse events affected 2.5% of the patients, while serious adverse events were identified in 25 cases (0.01%). Out of the 5970 patients with a complete VAS score for pain, the median VAS score was 8 (IQR 3) before treatment and 4 (IQR 3) after treatment. The mean reduction in pain measured by VAS was -4.1 ± 2.6 from the time before, to the evaluation after alfentanil administration. The administration frequency increased during the first year up to a steady level during the later part of the evaluation period.

CONCLUSIONS:

This study proposes that alfentanil represents a safe and efficacious alternative for addressing urgent pain relief within the prehospital emergency context. Alfentanil demonstrates efficacy in alleviating pain across various conditions, with a relatively low risk of adverse events or serious adverse events when administered cautiously.

01 Feb 2025·British Journal of Pharmacology

Slow dissociation kinetics of fentanyls and nitazenes correlates with reduced sensitivity to naloxone reversal at the μ‐opioid receptor

Article

Author: Kelly, Eamonn ; Santiago, Marina ; Cavallo, Damiana ; Henderson, Graeme ; Alhosan, Norah

Abstract:

Background and Purpose:

Fentanyls 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 Approach:

In 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 Results:

The 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 Implications:

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

Abstract:

Gastrointestinal 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.

2

News (Medical) associated with Alfentanil Hydrochloride

14 Mar 2025

·www.echemi.com

5 Key Updates on China's Fentanyl Control Amid US Tariffs

On February 1st, the United States announced a 10% tariff on products imported from China, citing concerns over the fentanyl crisis. In response, a spokesperson from the Ministry of Public Security emphasized that China maintains one of the strictest drug control policies in the world. As a signatory to the three UN drug control conventions, China has consistently upheld its international obligations and actively collaborates with countries, including the US, on drug enforcement efforts. In 2019, China took a humanitarian step by becoming the first country to classify all fentanyl-related substances under stringent controls, responding to US requests. Since this classification, China has not received reports of these substances being seized in the US. On March 12th, the National Medical Products Administration (NMPA) shared insights regarding China's management of fentanyl substances through a recently released white paper. The spokesperson addressed concerns about the production and export of fentanyl-related pharmaceuticals. Currently, four fentanyl-related drugs are approved for clinical use in China: fentanyl, sufentanil, remifentanil, and alfentanil. Three companies have been authorized to produce raw materials, while five are permitted to manufacture formulations. In 2024, China produced 100 kilograms of fentanyl raw materials, primarily for domestic medical use and export, with only 12.3 kilograms exported to countries like South Korea, Vietnam, and the Philippines. Notably, China has never exported fentanyl products to North America. All fentanyl-related drugs in China are classified as controlled narcotics, subjected to stringent regulations. The production and distribution of these drugs are closely monitored, with specific companies designated for manufacturing and fixed sales channels established. Export controls require permits, and international verification ensures the legality of trade before issuing export licenses. The NMPA will continue to enhance the supervision of fentanyl-related drug production and strictly regulate exports to prevent illegal channels and misuse, ensuring that medical needs are met responsibly.

Drug Approval

21 Jan 2025

·www.echemi.com

Humanwell Healthcare Secures Major Investment: A New Era Begins with Strategic Backing

After a three-month hiatus, leading domestic anesthetics producer Humanwell Healthcare has officially been "acquired" by a state-backed entity. On January 15, the company announced that it had signed a restructuring investment agreement with Zhaoshang Innovation Technology Group Co., Ltd. and its management team. This collaboration involves an investment of ¥11.8 billion, positioning Zhaoshang Innovation as the new controlling shareholder, with a 23.70% stake in Humanwell Healthcare. The restructuring investment will be executed in two phases. The first phase, covering 60% of the investment, will be paid upon the approval of the restructuring plan by the Wuhan Intermediate People’s Court. The remaining 40% will be paid after the completion of stock and voting rights transfers. Once this restructuring plan is finalized, Humanwell Healthcare will officially transition to state-owned control, a move that has significantly boosted its stock price, reaching ¥23.6 per share and a market capitalization of ¥38.52 billion. A Shift in Leadership: Hope for the "Anesthetic King" Founded in 1993, Humanwell Healthcare was once the dominant force in the anesthetic drugs sector. However, it has faced unprecedented challenges due to its former major shareholder, Dandai Technology, being mired in a debt crisis. Previously, six potential restructuring investors had passed the initial review, including three state-owned enterprises and three large local state-owned enterprises. Dandai Technology’s 23.7% stake in Humanwell Healthcare is currently frozen due to judicial actions. The entry of Zhaoshang Innovation brings a glimmer of hope, with the investment structured in three parts: Direct acquisition of 6% of Humanwell Healthcare’s shares. Indirect acquisition of another 6% through a new limited partnership in the Donghu New Technology Development Zone, with Zhaoshang Innovation as the general partner. Trust plan acquiring 11.70% of shares, with all voting rights delegated to Zhaoshang Innovation. Zhaoshang Innovation is controlled by China Merchants Group, a significant state-owned enterprise headquartered in Hong Kong. In 2023, China Merchants Group reported revenues of ¥924.4 billion and a net profit of ¥191.1 billion, showcasing its robust financial standing. Strategic Investment Amid Market Challenges Zhaoshang Innovation's substantial investment indicates its strategic interest in Humanwell Healthcare's industry-leading position in the pharmaceutical sector. Humanwell Healthcare is one of the few companies capable of producing a full range of fentanyl products and has established a strong foothold in various segments, including anesthetics and steroid hormones. According to the latest data, Humanwell Healthcare holds a 25.9% market share in the anesthetics market, making it the leading player. Its products, including alfentanil and hydromorphone, have a 100% market share, illustrating its dominance. In the past five years, Humanwell Healthcare has invested ¥4.6 billion in research and development, reflecting a commitment to innovation. In 2023, R&D expenses surpassed ¥1 billion, with a 9.2% increase in the first three quarters of 2024. The company has received approval for 1 traditional Chinese medicine and 17 chemical drug products, indicating a robust pipeline for future growth. Despite these positive developments, challenges remain. The competitive landscape is fierce, and the company must ensure that its R&D investments yield proportional returns. The support from Zhaoshang Innovation may provide the necessary impetus for Humanwell Healthcare to navigate these challenges successfully and emerge stronger. With Zhaoshang Innovation taking a controlling stake, Humanwell Healthcare's ownership issue has reached a significant resolution. This strategic investment from a state-owned entity sends positive signals to the market. However, the company still faces challenges related to market competition and R&D efficiency. Observers will be keen to see if Humanwell Healthcare can leverage this new partnership to overcome its obstacles and achieve a successful turnaround.

AcquisitionDrug Approval

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	United States	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	Phase 3	China	Jiangsu Nhwa Pharmaceutical Co., Ltd.	06 Jun 2018
Acute Pain	Phase 3	Czechia	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	rhebsopygn(fkexyubhxo) = amoodbkfkg bcvnugagmv (vlwcqnwirq ) View more	Positive	13 Aug 2024
				Alfentanil 25 µg/kg	robrprsvvw(gvxswefawz) = ygvwnsexuf vmyvagclce (drbixrllve )
NCT03359395 (CTgov)	Phase 4	-	100	Alfentanil (Alfentanil)	vvgylbwsje(abtuyvjwbv) = xhvzkwbsvb lbpqhumagw (qdgctipcut, 36.968) View more	-	08 Jul 2021
				Placebos (Placebo)	vvgylbwsje(abtuyvjwbv) = seyudjabuu lbpqhumagw (qdgctipcut, 33.50864) View more
NCT01008059 (CTgov)	Not Applicable	-	6	Alfentanil	qdphpcuman(tzqqpngsnb) = ixpcotbonp ppkpfkiayf (meehndsyfi, 15) View more	-	17 May 2019
NCT01094574 (CTgov)	Not Applicable	Pain \| Inflammation	10	Alfentanil (Alfentanil)	uuggwtmgjt(kqpcvhchpg) = nkbhepcypn nsgcdyvxcx (drwonmcnbr, 0.74) View more	-	24 Feb 2017
				Propranolol (Propranolol)	uuggwtmgjt(kqpcvhchpg) = xkblpypmyn nsgcdyvxcx (drwonmcnbr, 0.26) View more
NCT00997126 (CTgov)	Phase 4	Sedation	126	Propofol (Propofol)	uhnviofxpx = ygkeqlydtj qbouzpwbpc (uzhsykqnco, shogjvxqdf - rfocchzrmh) View more	-	27 Jan 2017
				Alfentanil (Alfentanil)	uhnviofxpx = kzycxqduco qbouzpwbpc (uzhsykqnco, lersvmphdk - cmfihynmmp) View more
NCT00672438 (CTgov)	Not Applicable	Pain	242	Alfentanil	dxwpxcwgiw(akmunwxiqt) = vgyxhhiibl mjiwdtefdi (mzoyothbnr, uxglnnnvwh - locdvmrthj) View more	-	21 Jul 2016
NCT01470170 (CTgov)	Phase 4	Hypoxia	173	Targeted controlled infusion+Propofol+normal saline+Alfentanil (Group1)	jonqhdskqr(ltrgvoigpu) = jxqiyalslh dgctwqtapt (zavmrvsqdk, 0.4) View more	-	13 Aug 2015
				Targeted controlled infusion+Propofol+normal saline+Alfentanil (Group 3)	jonqhdskqr(ltrgvoigpu) = tgkdffgggj dgctwqtapt (zavmrvsqdk, 0.4) View more
NCT00997113 (CTgov)	Phase 4	Sedation	20	propofol (Propofol)	jkdtacwbtz(rnjlfqongd) = dvujlzfzgq rxrewefrlm (ooikbnwggd, dfwcptoqfx - cleplhlpvs) View more	-	25 Sep 2014
				propofol+alfentanil (Propofol/Alfentanil)	jkdtacwbtz(rnjlfqongd) = vwausdcjst rxrewefrlm (ooikbnwggd, pwdqjbhyby - jxelkgymvh) View more
NCT00538850 (CTgov)	Phase 3	Cancer Pain \| Neoplasms	130	Placebo+Fentanyl sublingual spray	whdullgdnp(vofvutwnst) = ejnhdzyuzk vyebahcnjv (jkvlxyuecw, 458.8) View more	-	05 Mar 2014
Pubmed \| Clin J Pain	Not Applicable	Pain	-	Alfentanil 15 mcg/kg	heglxizkyg(hmivgzpdek) = aytlzxcxng hzshuufths (rjvqfyhhev, ±26.5)	-	01 Jan 2014