Fomepizole, 4-methylpyrazole (4-MP), is a competitive antagonist of alcohol dehydrogenase with a binding affinity >8000 times that of ethanol. Fomepizole's wide therapeutic dose range and safety profile confer several advantages over standard ethanol therapy for the treatment of toxic alcohol exposures, including the lack of ethanol-associated side effects[3]. Fomepizole is a safe and effective antidote in the treatment of ethylene glycol poisoning[4]. Male and pregnant Sprague-Dawley rats, which were obtained at 19 days gestation, were administered fomepizole 15 mg/kg intraperitoneally. Elevated concentrations of fomepizole were detected in the fetus following maternal administration. Fetal fomepizole concentrations were fivefold higher than maternal serum concentrations. The zero order elimination rate of fomepizole from maternal serum was 7.6 mol/L/h, which was slightly slower than the elimination rate in male rats (12.9 mol/L/h) [5]. 1 dose of fomepizole for severe DERs with hypotension unresponsive to fluid resuscitation or for angioedema unresponsive to antihistamines be administered[6]. Fomepizole may precipitate bradycardia and/or hypotension during hemodialysis. Monitor vital signs closely during and immediately after infusion[7].
Fomepizole/甲吡唑 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Mouse pancreatic acinar cells
100 µM
10 minutes
Investigated the effects of ethanol and palmitoleic acid (POA) on intracellular calcium concentration, showing that inhibition of oxidative metabolism by 4-MP (Fomepizole) converted transient calcium signals induced by ethanol/POA to sustained elevations, leading to mitochondrial depolarization and cellular necrosis. These effects were completely blocked by 3-BCP (a CEL inhibitor).
Gut. 2014 Aug;63(8):1313-24.
Primary human hepatocytes
10 mM or 20 mM
48 hours
Evaluate the protective effects of 4MP and NAC on APAP-induced cell death. 4MP at both concentrations significantly prevented APAP-induced cell death, while NAC was only partially effective at the highest concentration.
Arch Toxicol. 2021 Oct;95(10):3377-3391.
J774A.1 cells
2 mM
1 hour
To assess the effect of 4MP and JNK inhibitor on endotoxin-induced cell activation, results showed that the combination of 4MP and JNK inhibitor attenuated the release of NOx and IL-6 in an almost additive manner
Eur J Clin Invest. 2025 Jan;55(1):e14320.
Primary human kidney cells
2 mM
24 or 48 hours
Evaluate the protective effect of 4MP against APAP-induced cell death, results showed that 4MP significantly reduced APAP-induced cell death
Toxicology. 2023 Dec;500:153692.
Mouse epidermis extracts
1 mM
1 hour
To investigate the ability of mouse epidermis extracts to convert retinol to retinoic acid, showing effective oxidation of retinol to retinoic acid in the presence of NAD+.
Inhibition in vitro and in vivo. Biochem J.
Fomepizole/甲吡唑 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
CD1 mice
Alcoholic acute pancreatitis model
Intraperitoneal injection
10 mg/kg
Two injections at 1-hour intervals, observed for 24 hours
Evaluated the effects of 4-MP (Fomepizole) on alcoholic acute pancreatitis, showing that 4-MP exacerbated pancreatic damage and inflammation by inhibiting oxidative metabolism and promoting non-oxidative pathways. 3-BCP (a CEL inhibitor) significantly inhibited pancreatic FAEE elevation and ameliorated pancreatic damage and inflammation.
Gut. 2014 Aug;63(8):1313-24.
Mice
APAP-induced liver injury model
Intravenous
15 mg/kg and 10 mg/kg
Two doses 12 hours apart
Evaluate the protective effect of Fomepizole on APAP-induced liver injury, showing that Fomepizole effectively prevents liver injury by inhibiting Cyp2E1 and JNK activation.
Arch Toxicol. 2022 Feb;96(2):453-465
Mice
APAP-induced hepatotoxicity model
50 mg/kg
Immediately after APAP administration
To evaluate the protective effect of fomepizole against APAP hepatotoxicity, results showed that fomepizole significantly reduced plasma ALT elevations and centrilobular necrosis
Evaluate the protective effects of 4MP on APAP-induced hepatotoxicity. 4MP significantly attenuated liver injury at 24h and promoted recovery at 48h, which correlated with enhanced mitochondrial biogenesis and hepatocyte proliferation.
Arch Toxicol. 2021 Oct;95(10):3377-3391.
C57BL/6J mice
Non-obese metabolic dysfunction-associated steatotic liver disease (MASLD) model
Intraperitoneal injection
50 mg/kg body weight
Once weekly for 8 weeks
To assess the effect of 4MP on the development of MASLD, results showed that 4MP treatment significantly attenuated the increase in JNK phosphorylation and pro-inflammatory markers (e.g., IFNγ, IL-6, and 3-nitrotyrosine protein adducts) in liver tissue, but did not affect impairments in glucose tolerance or the increase in portal endotoxin levels
Eur J Clin Invest. 2025 Jan;55(1):e14320.
C57BL/6J mice
APAP-induced acute kidney injury model
Intraperitoneal injection
50 mg/kg
Single dose, euthanized at 24 hours
Evaluate the protective effect of 4MP against APAP-induced kidney injury, results showed that 4MP significantly reduced APAP-induced kidney injury and ER stress
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