Nitrosamines, ICH Q3A-Q3E, Global Substance Registration System (GSRS), N-nitroso dimethyl amine (NDMA), Drug substance life cycle
Curr Top Med Chem. 2024 Feb 6. doi: 10.2174/0115680266278636240125113509. Online ahead of print.ABSTRACTSince their discovery in valsartan-containing drugs, nitrosamine impurities have emerged as a significant safety problem in pharmaceutical products, prompting extensive recalls and suspensions. Valsartan, candesartan, irbesartan, olmesartan, and other sartans have been discovered to have additional nitrosamine impurities, such as N-nitroso-N-methyl-4-aminobutyric acid (NMBA), N-nitroso-Di-isopropyl amine (NDIPA), N-nitroso-Ethyl-Isopropyl amine (NEIPA), and N-nitroso-Diethyl amine (NDEA). Concerns about drug safety have ...
Source: Current Topics in Medicinal Chemistry - February 7, 2024 Category: Chemistry Authors: Darshan Bhirud Gyan Agrawal Harshil Shah Artiben Patel Mahesh B Palkar Sankha Bhattacharya Bhupendra G Prajapati Source Type: research

Inhibitors of gastric acid secretion increase oxidative stress and matrix metalloproteinase-2 activity leading to vascular remodeling
This study aimed at examining whether treatment with the H2RB ranitidine promotes oxidative stress resulting in vascular MMP activation and corresponding functional and structural alterations in the vasculature, as compared with those found with the PPI omeprazole. Male Wistar rats were treated (4 weeks) with vehicle (2% tween 20), omeprazole (10 mg/Kg/day; i.p.) or ranitidine (100 mg/Kg/day; gavage). Then the aorta was collected to perform functional, biochemical, and morphometric analysis. Both ranitidine and omeprazole increased gastric pH and oxidative stress assessed in situ with the fluorescent dye dihydroethidium (D...
Source: Molecular and Cellular Biochemistry - February 1, 2024 Category: Biochemistry Authors: Renato C Nogueira J éssica M Sanches-Lopes Gustavo H Oliveira-Paula Jose E Tanus-Santos Source Type: research

In Silico Prediction of N-Nitrosamine Formation Pathways of Pharmaceutical Products
In this study, we first predicted the degradation pathways and impurities of model pharmaceuticals, namely gliclazide and indapamide, in silico using an expert-knowledge software. Second, we verified the prediction results with a demonstration test, which confirmed that N-nitrosamines formed from the degradation of gliclazide and indapamide in the presence of hydrogen peroxide, especially under alkaline conditions. Furthermore, the pathways by which degradation products formed were determined using ranitidine, a compound previously demonstrated to generate NDMA. The prediction indicated that a ranitidine-related compound s...
Source: Chemical and Pharmaceutical Bulletin - January 31, 2024 Category: Drugs & Pharmacology Authors: Genichiro Tsuji Takashi Kurohara Takuji Shoda Hidetomo Yokoo Takahito Ito Sayaka Masada Nahoko Uchiyama Eiichi Yamamoto Yosuke Demizu Source Type: research

Histamine H < sub > 2 < /sub > -receptor antagonism improves conduit artery endothelial function and reduces plasma aldosterone level without lowering arterial blood pressure in angiotensin II-hypertensive mice
Pflugers Arch. 2024 Mar;476(3):307-321. doi: 10.1007/s00424-024-02909-0. Epub 2024 Jan 27.ABSTRACTAldosterone through the mineralocorticoid receptor MR has detrimental effects on cardiovascular disease. It reduces the bioavailability of nitric oxide and impairs endothelium-dependent vasodilatation. In resistance arteries, aldosterone impairs the sensitivity of vascular smooth muscle cells to nitric oxide by promoting the local secretion of histamine which activates H2 receptors. The present experiments tested in vivo and ex vivo the hypothesis that systemic H2-receptor antagonism reduces arterial blood pressure and improve...
Source: Pflugers Archiv : European Journal of Physiology - January 27, 2024 Category: Physiology Authors: Kasper B Assersen Boye L Jensen Camilla Enggaard Paul M Vanhoutte Pernille B L Hansen Source Type: research

Systematic identification and repurposing of FDA-approved drugs as antibacterial agents against Streptococcus pyogenes: In silico and in vitro studies
In this study, 1826 FDA approved drugs have been identified through high-throughput virtual screening. Free Energy Perturbation (FEP) based binding free energy calculations have been performed at the final step of the virtual screening funnel to ensure high accuracy in silico results. Three compounds identified have been tested for susceptibility of S. pyogenes MTCC 442 strain and two antibiotic-resistant clinical isolates of S. pyogenes using microdilution assay. Among the three, two drugs Amlodipine Besylate (Amd) and Ranitidine hydrochloride (Rnt) have shown inhibition against all the tested strains and its mechanism of...
Source: International Journal of Biological Macromolecules - December 15, 2023 Category: Biochemistry Authors: Judith Gracia Damodharan Perumal Prabu Dhandapani Preethi Ragunathan Source Type: research

Systematic identification and repurposing of FDA-approved drugs as antibacterial agents against Streptococcus pyogenes: In silico and in vitro studies
In this study, 1826 FDA approved drugs have been identified through high-throughput virtual screening. Free Energy Perturbation (FEP) based binding free energy calculations have been performed at the final step of the virtual screening funnel to ensure high accuracy in silico results. Three compounds identified have been tested for susceptibility of S. pyogenes MTCC 442 strain and two antibiotic-resistant clinical isolates of S. pyogenes using microdilution assay. Among the three, two drugs Amlodipine Besylate (Amd) and Ranitidine hydrochloride (Rnt) have shown inhibition against all the tested strains and its mechanism of...
Source: International Journal of Biological Macromolecules - December 15, 2023 Category: Biochemistry Authors: Judith Gracia Damodharan Perumal Prabu Dhandapani Preethi Ragunathan Source Type: research

Drug-induced tumoral disease: A global pharmacovigilance database analysis
DISCUSSION: Our results show that the main pharmacological mechanisms are associated with ranitidine (link with levels of N-nitrosodimethylamine in ranitidine-based drugs), gene-activating drugs (pioglitazone: link with agonist effects on PPAR-γ gene activation), various pharmacological families with immunosuppressive effects (protein kinase inhibitors, immunomodulators, azathioprine, etc.), certain types of protein kinase inhibitors whose oncogenic mechanisms remain unclear (regorafenib, sorafenib, imatinib, ibrutinib, etc.), and hormone antagonists (tamoxifen, letrozole). Special monitoring of patients exposed to these ...
Source: Therapie - December 2, 2023 Category: Psychiatry & Psychology Authors: Yoann Zelmat Fabien Despas Source Type: research

Drug-induced tumoral disease: A global pharmacovigilance database analysis
DISCUSSION: Our results show that the main pharmacological mechanisms are associated with ranitidine (link with levels of N-nitrosodimethylamine in ranitidine-based drugs), gene-activating drugs (pioglitazone: link with agonist effects on PPAR-γ gene activation), various pharmacological families with immunosuppressive effects (protein kinase inhibitors, immunomodulators, azathioprine, etc.), certain types of protein kinase inhibitors whose oncogenic mechanisms remain unclear (regorafenib, sorafenib, imatinib, ibrutinib, etc.), and hormone antagonists (tamoxifen, letrozole). Special monitoring of patients exposed to these ...
Source: Therapie - December 2, 2023 Category: Psychiatry & Psychology Authors: Yoann Zelmat Fabien Despas Source Type: research

Drug-induced tumoral disease: A global pharmacovigilance database analysis
DISCUSSION: Our results show that the main pharmacological mechanisms are associated with ranitidine (link with levels of N-nitrosodimethylamine in ranitidine-based drugs), gene-activating drugs (pioglitazone: link with agonist effects on PPAR-γ gene activation), various pharmacological families with immunosuppressive effects (protein kinase inhibitors, immunomodulators, azathioprine, etc.), certain types of protein kinase inhibitors whose oncogenic mechanisms remain unclear (regorafenib, sorafenib, imatinib, ibrutinib, etc.), and hormone antagonists (tamoxifen, letrozole). Special monitoring of patients exposed to these ...
Source: Therapie - December 2, 2023 Category: Psychiatry & Psychology Authors: Yoann Zelmat Fabien Despas Source Type: research

Drug-induced tumoral disease: A global pharmacovigilance database analysis
DISCUSSION: Our results show that the main pharmacological mechanisms are associated with ranitidine (link with levels of N-nitrosodimethylamine in ranitidine-based drugs), gene-activating drugs (pioglitazone: link with agonist effects on PPAR-γ gene activation), various pharmacological families with immunosuppressive effects (protein kinase inhibitors, immunomodulators, azathioprine, etc.), certain types of protein kinase inhibitors whose oncogenic mechanisms remain unclear (regorafenib, sorafenib, imatinib, ibrutinib, etc.), and hormone antagonists (tamoxifen, letrozole). Special monitoring of patients exposed to these ...
Source: Therapie - December 2, 2023 Category: Psychiatry & Psychology Authors: Yoann Zelmat Fabien Despas Source Type: research

A robust analytical method for simultaneous quantification of 13 low-molecular-weight N-Nitrosamines in various pharmaceuticals based on solid phase extraction and liquid chromatography coupled to high-resolution mass spectrometry
Eur J Pharm Sci. 2023 Nov 9:106633. doi: 10.1016/j.ejps.2023.106633. Online ahead of print.ABSTRACTRecently, the potentially highly carcinogenic N-nitrosamines (NAs) have become the focus of pharmaceutical regulatory authorities, the pharmaceutical industry and researchers because trace amounts have been detected in some drug products (DPs), resulting in drug supply shortages. In the absence of sufficient analytical methods for the determination of multiple regulated low-molecular-weight NAs in various DPs, a robust, selective, sensitive and accurate method based on sample preparation by solid-phase extraction, followed by...
Source: European Journal of Pharmaceutical Sciences - November 11, 2023 Category: Drugs & Pharmacology Authors: Timeja Planin šek Parfant Taja Skube Robert Ro škar Source Type: research

A robust analytical method for simultaneous quantification of 13 low-molecular-weight N-Nitrosamines in various pharmaceuticals based on solid phase extraction and liquid chromatography coupled to high-resolution mass spectrometry
Eur J Pharm Sci. 2023 Nov 9:106633. doi: 10.1016/j.ejps.2023.106633. Online ahead of print.ABSTRACTRecently, the potentially highly carcinogenic N-nitrosamines (NAs) have become the focus of pharmaceutical regulatory authorities, the pharmaceutical industry and researchers because trace amounts have been detected in some drug products (DPs), resulting in drug supply shortages. In the absence of sufficient analytical methods for the determination of multiple regulated low-molecular-weight NAs in various DPs, a robust, selective, sensitive and accurate method based on sample preparation by solid-phase extraction, followed by...
Source: European Journal of Pharmaceutical Sciences - November 11, 2023 Category: Drugs & Pharmacology Authors: Timeja Planin šek Parfant Taja Skube Robert Ro škar Source Type: research

Prescription ranitidine use and population exposure in 6 Canadian provinces, 1996 to 2019: a serial cross-sectional analysis
CMAJ Open. 2023 Nov 7;11(6):E1033-E1040. doi: 10.9778/cmajo.20220131. Print 2023 Nov-Dec.ABSTRACTBACKGROUND: Ranitidine was the most prescribed histamine-2 receptor antagonist (H2RA) in Canada when recalled in 2019 because of potential carcinogenicity. We sought to compare geographic and temporal patterns in use of prescription ranitidine and 3 other HRAs and estimated population exposure to ranitidine in 6 provinces between 1996 and 2019.METHODS: This population-based serial cross-sectional study used prescription claims for H2RAs dispensed from community pharmacies in Nova Scotia, Ontario, Manitoba, Saskatchewan, Alberta...
Source: cmaj - November 7, 2023 Category: General Medicine Authors: Adrian R Levy David Stock J Michael Paterson Hala Tamim Dan Chateau Jacqueline Quail Paul E Ronksley Greg Carney Pauline Reynier Laura Targownik Canadian Network for Observational Drug Effect Studies (CNODES) Investigators Source Type: research

Prescription ranitidine use and population exposure in 6 Canadian provinces, 1996 to 2019: a serial cross-sectional analysis
CMAJ Open. 2023 Nov 7;11(6):E1033-E1040. doi: 10.9778/cmajo.20220131. Print 2023 Nov-Dec.ABSTRACTBACKGROUND: Ranitidine was the most prescribed histamine-2 receptor antagonist (H2RA) in Canada when recalled in 2019 because of potential carcinogenicity. We sought to compare geographic and temporal patterns in use of prescription ranitidine and 3 other HRAs and estimated population exposure to ranitidine in 6 provinces between 1996 and 2019.METHODS: This population-based serial cross-sectional study used prescription claims for H2RAs dispensed from community pharmacies in Nova Scotia, Ontario, Manitoba, Saskatchewan, Alberta...
Source: cmaj - November 7, 2023 Category: General Medicine Authors: Adrian R Levy David Stock J Michael Paterson Hala Tamim Dan Chateau Jacqueline Quail Paul E Ronksley Greg Carney Pauline Reynier Laura Targownik Canadian Network for Observational Drug Effect Studies (CNODES) Investigators Source Type: research

Prescription ranitidine use and population exposure in 6 Canadian provinces, 1996 to 2019: a serial cross-sectional analysis
CMAJ Open. 2023 Nov 7;11(6):E1033-E1040. doi: 10.9778/cmajo.20220131. Print 2023 Nov-Dec.ABSTRACTBACKGROUND: Ranitidine was the most prescribed histamine-2 receptor antagonist (H2RA) in Canada when recalled in 2019 because of potential carcinogenicity. We sought to compare geographic and temporal patterns in use of prescription ranitidine and 3 other HRAs and estimated population exposure to ranitidine in 6 provinces between 1996 and 2019.METHODS: This population-based serial cross-sectional study used prescription claims for H2RAs dispensed from community pharmacies in Nova Scotia, Ontario, Manitoba, Saskatchewan, Alberta...
Source: cmaj - November 7, 2023 Category: General Medicine Authors: Adrian R Levy David Stock J Michael Paterson Hala Tamim Dan Chateau Jacqueline Quail Paul E Ronksley Greg Carney Pauline Reynier Laura Targownik Canadian Network for Observational Drug Effect Studies (CNODES) Investigators Source Type: research