Delving into the Latest Updates on Azelnidipine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Azelnidipine (JP17/INN)

+ [5]

Target

L-type calcium channel

Mechanism

L-type calcium channel blockers(Voltage-gated L-type calcium channel blockers)

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Hypertension

Inactive Indication-

Originator Organization

Daiichi Sankyo Co., Ltd.

Active Organization

Daiichi Sankyo Co., Ltd.

Lianyungang Runzhong Pharmaceutical Co., Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

JP (31 Jan 2003),

Hypertension

Regulation-

Login to view timeline

Structure/Sequence

Molecular FormulaC33H34N4O6

InChIKeyZKFQEACEUNWPMT-UHFFFAOYSA-N

CAS Registry123524-52-7

AbstractA spectrofluorimetric method using fluorescent carbon dots (CDs) was developed for the selective detection of azelnidipine (AZEL) pharmaceutical in the presence of other drugs. In this study, N‐doped CDs (N‐CDs) were synthesized through a single‐step hydrothermal process, using citric acid and urea as precursor materials. The prepared N‐CDs showed a highly intense blue fluorescence emission at 447 nm, with a photoluminescence quantum yield of ~21.15% and a fluorescence lifetime of 0.47 ns. The N‐CDs showed selective fluorescence quenching in the presence of all three antihypertensive drugs, which was used as a successful detection platform for the analysis of AZEL. The photophysical properties, UV–vis light absorbance, fluorescence emission, and lifetime measurements support the interaction between N‐CDs and AZEL, leading to fluorescence quenching of N‐CDs as a result of ground‐state complex formation followed by a static fluorescence quenching phenomenon. The detection platform showed linearity in the range 10–200 μg/ml (R2 = 0.9837). The developed method was effectively utilized for the quantitative analysis of AZEL in commercially available pharmaceutical tablets, yielding results that closely align with those obtained from the standard method (UV spectroscopy). With a score of 0.76 on the ‘Analytical GREEnness (AGREE)’ scale, the developed analytical method, incorporating 12 distinct green analytical chemistry components, stands out as an important technique for estimating AZEL.

01 Apr 2024·Drug Metabolism and Pharmacokinetics

Physiologically based pharmacokinetic modeling to predict the clinical effect of azole antifungal agents as CYP3A inhibitors on azelnidipine pharmacokinetics

Article

Author: Watanabe, Akiko ; Kotsuma, Masakatsu

In this study, a physiologically based pharmacokinetic (PBPK) model of the cytochrome P450 3A (CYP3A) substrate azelnidipine was developed using in vitro and clinical data to predict the effects of azole antifungals on azelnidipine pharmacokinetics. Modeling and simulations were conducted using the Simcyp™ PBPK simulator. The azelnidipine model consisted of a full PBPK model and a first-order absorption model. CYP3A was assumed as the only azelnidipine elimination route, and CYP3A clearance was optimized using the pharmacokinetic profile of single-dose 5-mg azelnidipine in healthy participants. The model reproduced the results of a clinical drug-drug interaction study and met validation criteria. PBPK model simulations using azole antifungals (itraconazole, voriconazole, posaconazole, fluconazole, fosfluconazole) and azelnidipine or midazolam (CYP3A index substrate) were performed. Increases in the simulated area under the plasma concentration-time curve from time zero extrapolated to infinity with inhibitors were comparable between azelnidipine (range, 2.11-6.47) and midazolam (range, 2.26-9.22), demonstrating that azelnidipine is a sensitive CYP3A substrate. Increased azelnidipine plasma concentrations are expected when co-administered with azole antifungals, potentially affecting azelnidipine safety. These findings support the avoidance of azole antifungals in patients taking azelnidipine and demonstrate the utility of PBPK modeling to inform appropriate drug use.

01 Apr 2024·BMJ Case Reports

Acute quadruple extremity compartment syndrome due to angio-oedema after polypharmacy overdose including olmesartan medoxomil, telmisartan and vildagliptin

Article

Author: Kono, Yumi ; Fujii, Motoki ; Hayashi, Yoshiro ; Takimoto, Kohei

This case report describes a rare manifestation of acute compartment syndrome (ACS) involving all four extremities, precipitated by angio-oedema in a middle-aged woman who consumed an overdose of multiple medications: nifedipine, azelnidipine, amlodipine besylate, olmesartan medoxomil, telmisartan, esaxerenone and vildagliptin. She presented with haemodynamic instability, necessitating intubation. Despite stabilising haemodynamic parameters within 24 hours, she manifested escalating extremity oedema. At 52 hours after ingestion, mottled skin was observed, along with necrotic alterations in the swollen hands and compartment pressures exceeding 30 mm Hg in all extremities. ACS was diagnosed, leading to fasciotomies. The aetiology is postulated to be drug-induced angio-oedema, possibly intensified by the concurrent overdose of olmesartan medoxomil, telmisartan and vildagliptin, each of which has a risk of angio-oedema even at standard dosages. This scenario is a very rare case caused by drug-induced angio-oedema, which underscores the importance of vigilant monitoring to detect ACS in patients with progressing limb oedema.

100 Deals associated with Azelnidipine

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D01145	Azelnidipine	C08CA	DB09230

R&D Status

10 top approved records.

Login

to view more data

Indication	Country/Location	Organization	Date
Hypertension	JP	Daiichi Sankyo Co., Ltd.	31 Jan 2003

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


GUARD study (ESH2012)	Not Applicable	-	-	Olmesartan + Azelnidipine	(ftjjgjuymt) = bsznfhmhxt hygnuwxbew (vxyysqwwlf )	Positive	01 Sep 2012
				Olmesartan + Trichlormethiazide	(ftjjgjuymt) = anjhutrtdm hygnuwxbew (vxyysqwwlf )
555 (ESH2012)	Not Applicable	Hypertension	-	Amlodipine	(uvlodqkhio) = crjdgotcyf snmnmakwtq (dtchqvugaz ) View more	Positive	01 Sep 2012
				Azelnidipine	(uvlodqkhio) = pfzpoiwsim snmnmakwtq (dtchqvugaz ) View more
201 (ESH2012)	Not Applicable	Hypertension	-	Azelnidipine	(usrjxprnvs) = ubcgqkmwjk apmxuuhvpo (qlytqpyoom ) View more	Positive	01 Sep 2012
				Amlodipine	(usrjxprnvs) = qtmbcqhtdi apmxuuhvpo (qlytqpyoom ) View more
PP.1.32 (ESH2010)	Not Applicable	Functional disorder	-	Azelnidipine 0.3 mg/kg	wexgtffjze(yualgyuvfj) = trgmqmjjds yhnjrminyh (mrgqfluzap, 5) View more	Positive	01 Jun 2010
				Labetalol 3 mg/kg	wexgtffjze(yualgyuvfj) = dxxqyahlfw yhnjrminyh (mrgqfluzap, 4) View more