Delving into the Latest Updates on Acetylcysteine/Mesalazine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Acetylcysteine/mesalamine, Mesalamine/N-acetylcysteine, Mesalazine/acetylcysteine

+ [5]

Target

Free radicals x PP2A

Mechanism

Free radicals inhibitors, PP2A inhibitors(Protein phosphatase 2A inhibitors)

Therapeutic Areas

Digestive System Disorders

Active Indication-

Inactive Indication

Colitis, UlcerativeCrohn DiseaseUlcerative proctitis

Originator Organization

University of Oklahoma Health Sciences Center

Active Organization-

Inactive Organization

Altheus Therapeutics, Inc.

University of Oklahoma Health Sciences Center

Drug Highest PhasePendingPhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC5H9NO3S

InChIKeyPWKSKIMOESPYIA-BYPYZUCNSA-N

CAS Registry616-91-1

View All Structures (2)

This double-blind, randomized, comparator-controlled Phase II study is designed to establish the safety and efficacy of Zoenasa Rectal Gel compared to mesalamine enema in subjects with left-sided ulcerative colitis, as measured by the modified ulcerative colitis disease activity index (UCDAI), over 6 weeks of treatment. In this study, two cohorts of subjects will receive either Zoenasa-1:4 (1.0g NAC; 4.0g 5-ASA) investigational drug enema therapy or comparator mesalamine enema (4.0g 5-ASA). The study will enroll subjects randomized equally into the 2 cohorts. Each cohort will enroll approximately 60 subjects. The two arms of the trial will be enrolled concurrently in a randomized fashion.

Start Date01 Jun 2012

Sponsor / Collaborator

Altheus Therapeutics, Inc.

NCT01020708 / CompletedPhase 1

A Phase I Double-blind, Randomized, Comparator-controlled Study of the Safety and Tolerability of N-acetylcysteine Plus Mesalamine Enema in Subjects With Left-sided Ulcerative Colitis

This Phase I study will be a closely monitored trial of a small number of subjects to establish, preliminarily, the tolerability and safety of two ALTH12 enema formulations: ALTH12-1:4 and ALTH12-2:4. The study will be conducted in two parts. The first part will be the assessment of the safety and tolerability of a single dose of ALTH12-1:4 or the comparator, mesalamine (4.0g 5-ASA) followed by an assessment of repeated administrations of study drug (ALTH12-1:4 or comparator) for 6 weeks. The second part will be the same assessment for ALTH12-2:4. Three subjects will be enrolled in each cohort: 2 to receive ALTH12 enema therapy and 1 subject to receive comparator enema therapy. A total of up to 9 patients will be enrolled in this study, allowing for up to 3 replacement or additional patients.

Start Date01 Nov 2009

Sponsor / Collaborator

Altheus Therapeutics, Inc.

100 Clinical Results associated with Acetylcysteine/Mesalazine

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100 Translational Medicine associated with Acetylcysteine/Mesalazine

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100 Patents (Medical) associated with Acetylcysteine/Mesalazine

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5

Literatures (Medical) associated with Acetylcysteine/Mesalazine

01 Jun 2022·Journal of Controlled ReleaseQ1 · MEDICINE

Population pharmacokinetics and IVIVC for mesalazine enteric-coated tablets

Q1 · MEDICINE

Article

Author: Yan, Xiaoyu ; Zhang, Yufeng ; Wo, Siu Kwan ; Zuo, Zhong ; Leng, Wei ; Gao, Fang

Although in-vivo bioequivalence (BE) study serves as a golden standard for establishing interchangeability of oral dosage forms, it remains challenging for products with high inter-subject variability such as mesalazine enteric-coated tablet to fulfil the BE criteria set by regulatory authorities. Mesalazine, as a BCS class IV drug, targets to be delivered to distal ileum or colon with a pH-sensitive polymer coating for the remission of ulcerative colitis. Through population pharmacokinetic (PK) analysis and in-vitro in-vivo correlation (IVIVC) modeling on the dissolution and BE data of a generic enteric-coated product (EM) and its reference Salofalk® 250 mg tablet (SM), we for the first time revealed the underlying mechanism of the high inter-subject variability for such delayed-release formulation. It was also noted that the in-vivo start time of absorption (T_s) for EM and SM was positively correlated with their in-vitro lag time (T_lag) under the USP three-stage dissolution condition and reversely correlated with their in-vivo bioavailability. The varied oral bioavailability of mesalazine enteric-coated tablet was mainly due to the varied N-acetyltransferase activities along GI tract. Although such extensive intestinal first-pass metabolism with large individual differences led to a significant variation of mesalazine C_max (coefficient of variation: 60-63.5%) and AUC_0-t (coefficient of variation: 37.5-46.9%), the corresponding variations in the total absorbed mesalazine (mesalazine and its metabolite N-acetyl mesalazine) were significantly reduced by 12 to 45%. Since the BE purpose for mesalazine enteric-coated tablet focused on their comparable safety profiles, total absorbed mesalazine was recommended to be adopted for the development of the IVIVC model and BE evaluation for EM. All in all, our model-based approach has not only successfully identified the key factors that affect the BE of EM to guide its further formulation optimization, but also demonstrated the indispensable role of modeling in the development of generic pharmaceutical product at its early stages.

01 May 2022·International Journal of PharmaceuticsQ2 · MEDICINE

The effect of esomeprazole on the upper GI tract release and systemic absorption of mesalazine from colon targeted formulations

Q2 · MEDICINE

Article

Author: Van Camp, Arno ; Augustijns, Patrick ; Brouwers, Joachim ; Vanuytsel, Tim

The aim of the present study was to investigate the effect of coadministration of the proton pump inhibitor (PPI) esomeprazole on the upper GI tract behavior and systemic exposure of mesalazine from two mechanistically different colon targeted delivery systems: Claversal (pH-dependent release) and Pentasa (prolonged release). To this end, gastric, jejunal and systemic concentrations of mesalazine and its metabolite N-acetyl mesalazine were monitored in 5 healthy volunteers following oral intake of Pentasa or Claversal with or without PPI pre-treatment (cross-over study). Our exploratory study demonstrated that pre-treatment with a PPI may affect the release and absorption of mesalazine from formulations with different modified release mechanisms. Upon intake of Claversal, the onset of mesalazine absorption was accelerated substantially by PPI pre-treatment. While the PPI-induced increase in pH initiated the disintegration process already in the upper GI tract, the release of mesalazine started beyond the proximal jejunum. Upon intake of Pentasa, PPI pre-treatment seemed to increase the systemic exposure, even though the underlying mechanism could not be revealed yet. The faster release of mesalazine in the GI tract and/or the increased systemic absorption following PPI pre-treatment may reduce the ability of mesalazine to reach the colon. Future research assessing mesalazine disposition in the lower GI tract is warranted.

01 Jan 1994·Folia Pharmacologica Japonica

Effect of mesalazine, an agent for the treatment of idiopathic inflammatory bowel disease, on reactive oxygen metabolites and LTB4 formation.

Article

Author: Taniguchi, Sugure ; Kinoshita, Nobuhiro ; Kawase, Shigeo ; Sato, Masako ; Sugai, Toshiji ; Nakamaru, Koichi

Mesalazine microgranules (Pentasa) were developed as a drug for idiopathic inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. In this study, we examined the effect of mesalazine on radical scavenging, lipid peroxidation and the formation of LTB4. Mesalazine reduced the free radical 1,1-diphenyl-2-picrylhydrazyl with an IC50 value of 9.5 microM. It scavenged hydrogen peroxide and hypochlorite (IC50: 0.7 microM and 37.0 microM, respectively), but had no effect on superoxide. Lipid peroxidation in rat liver microsomes was inhibited by mesalazine (IC50: 12.6 microM). Mesalazine significantly inhibited (P < 0.01) gastric mucosal lipid peroxidation induced by ischemia and reperfusion in rats at a dose of 50 mg/kg, p.o. Mesalazine also inhibited the formation of LTB4 in rat peritoneal neutrophils (IC50: 44.9 microM). N-Acetyl-mesalazine, the metabolite of mesalazine, had no effect on radical scavenging and lipid peroxidation. Only a high concentration (1 mM) of the metabolite inhibited the formation of LTB4. These studies suggest that mesalazine inhibits cell injury in the inflamed mucosa by scavenging reactive oxygen metabolites and prevents the invasion of neutrophils by inhibition of LTB4 formation.

100 Deals associated with Acetylcysteine/Mesalazine

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Colitis, Ulcerative	Phase 3	-	University of Oklahoma Health Sciences Center	-
Crohn Disease	Phase 3	US	Altheus Therapeutics, Inc.	-
Ulcerative proctitis	Phase 3	US	Altheus Therapeutics, Inc.	-