体外活性： 激酶测定： 细胞测定：

甲吡唑（4-甲基吡唑；25 mg/kg；IP）预处理可延长 CD-1 小鼠中乙醇的神经行为毒性[4]。

Animal/Disease Models: Male CD-1 mice weighing 18-25 g[4]
Doses: 25 mg/kg
Route of Administration: IP; single dose
Experimental Results: diminished the dose of ethanol (1-5 g/kg; IP) at which 50% of the animals failed a particular outcome test (toxic dose 50; TD50).

Absorption, Distribution and Excretion
Rapid and complete
In healthy volunteers, only 1-3.5% of the administered dose of Antizol® (7-20 mg/kg oral and IV) was excreted unchanged in the urine, indicating that metabolism is the major route of elimination. In humans, the primary metabolite of Antizol® is 4-carboxypyrazole (approximately 80-85% of administered dose), which is excreted in the urine. The metabolites of Antizol® are excreted renally.
0.6 to 1.02 L/kg

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Metabolism / Metabolites
Primarily hepatic. the primary metabolite is 4-carboxypyrazole (approximately 80 to 85% of an administered dose). Minor metabolites include 4-hydroxymethylpyrazole and the N -glucuronide conjugates of 4-carboxypyrazole and 4-hydroxymethylpyrazole.

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Biological Half-Life
The plasma half-life of Antizol varies with dose, even in patients with normal renal function, and has not been calculated.

[1]. Casavant MJ. Fomepizole in the treatment of poisoning. Pediatrics. 2001 Jan;107(1):170.

[2]. Adverse drug events associated with the antidotes for methanol and ethylene glycol poisoning: a comparison of ethanol and fomepizole. Ann Emerg Med. 2009 Apr;53(4):439-450.e10.

[3]. Use of fomepizole as an adjunct in the treatment of acetaminophen overdose: a case series. Toxicology Communications. Volume 4, 2020 - Issue 1.

[4]. Effects of 4-methylpyrazole on ethanol neurobehavioral toxicity in CD-1 mice. Acad Emerg Med. 2004 Aug;11(8):820-6.

Fomepizole is a member of the class of pyrazoles that is 1H-pyrazole substituted by a methyl group at position 4. It has a role as an antidote, a protective agent and an EC 1.1.1.1 (alcohol dehydrogenase) inhibitor. It derives from a hydride of a 1H-pyrazole.
Fomepizole is used as an antidote in confirmed or suspected methanol or ethylene glycol poisoning. Fomepizole is a competitive inhibitor of alcohol dehydrogenase, the enzyme that catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites.
Fomepizole is an Antidote.
Fomepizole is a pyrazole with competitive alcohol dehydrogenase inhibitor activity. Fomepizole prevents the metabolism of ethylene glycol and methanol by alcohol dehydrogenase, thereby inhibiting the formation of their toxic metabolites, glycolate and oxalate (from ethylene glycol), and formic acid (from methanol). Fomepizole is indicated for use as an antidote in ethylene glycol and methanol poisoning. (NCI05)
A pyrazole and competitive inhibitor of ALCOHOL DEHYDROGENASE that is used for the treatment of poisoning by ETHYLENE GLYCOL or METHANOL.

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Drug Indication
Antizol is indicated as an antidote for ethylene glycol (such as antifreeze) or methanol poisoning, or for use in suspected ethylene glycol or methanol ingestion, either alone or in combination with hemodialysis

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Mechanism of Action
Antizol (fomepizole) is a competitive inhibitor of alcohol dehydrogenase. Alcohol dehydrogenase catalyzes the oxidation of ethanol to acetaldehyde. Alcohol dehydrogenase also catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites.

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Pharmacodynamics
Fomepizole is a competitive inhibitor of alcohol dehydrogenase, the enzyme that catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites. Ethylene glycol is first metabolized to glycoaldehyde which then undergoes further oxidation to glycolate, glyoxylate, and oxalate. Glycolate and oxalate are primarily responsible for metabolic acidosis and renal damage seen in ethylene glycol toxicity. {01}{03} Methanol is first metabolized to formaldehyde and then undergoes subsequent oxidation via formaldehyde dehydrogenase to become formic acid. It is formic acid that is primarily responsible for the metabolic acidosis and visual disturbances that are associated with methanol poisoning.

C4H6N2

82.1

82.053

7554-65-6

Fomepizole hydrochloride;56010-88-9

3406

Off-white to light yellow <13°C powder,>13°C liquid

1.1±0.1 g/cm3

243.6±0.0 °C at 760 mmHg

13°C

96.1±0.0 °C

0.1±0.4 mmHg at 25°C

1.523

0.78

28.68

1

1

0

6

44.8

0

N1([H])C([H])=C(C([H])=N1)C([H])([H])[H]

RIKMMFOAQPJVMX-UHFFFAOYSA-N

InChI=1S/C4H6N2/c1-4-2-5-6-3-4/h2-3H,1H3,(H,5,6)

4-methyl-1H-pyrazole

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.5 mg/mL (30.45 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (30.45 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (30.45 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 140 mg/mL (1705.24 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。