BENZNIDAZOLE (Ro 07-1051)   中文名称: 苄硝唑

Trypanosoma

当感染克氏锥虫 Tulahuen 株或 SGO-Z12 分离株的小鼠接受苯并咪唑（100 mg/kg/天，口服，30 天）治疗时，结果包括心电图改变减少、心脏受体的亲和力和密度改变减少，以及心脏中一些孤立的纤维化区域[1]。

Animal Model: Mice infected with Trypanosoma cruzi Tulahuen strain or SGO-Z12[1]
Dosage: 100 mg/kg/day
Administration: Orally for 30 days
Result: reduced the number of changes in the affinity and density of cardiac receptors, reduced the number of isolated cardiac fibrosis regions, and decreased electrocardiographic alterations.

Absorption, Distribution and Excretion
Benznidazole has a bioavailability of 91.7% and a Tmax of 2.93 h.
The metabolites of benznidazole appear to be primarily exreted in the urine.
The apparent volume of distribution is 39.19 L.
The apparent oral clearance is 2.04 L/h.

---

Metabolism / Metabolites
Benznidazole is metabolized by nitroreductases in *Trypanosoma cruzi* and by cytochrome P450 enzymes.

---

Biological Half-Life
The half life of elimination is 13.27 h.

Hepatotoxicity
Benznidazole therapy is associated with an appreciable rate of serum enzyme elevations, found in at least 10% of patients. The abnormalities, however, are generally mild, transient and without accompanying symptoms or jaundice. In clinical trials there were no reported instances of clinically apparent liver injury with jaundice attributed to benznidazole. However, since its approval and more widescale use, there have been several case reports of drug rash with eosinophilia and systemic symptoms (DRESS syndrome) accompanied by serum enzyme elevations associated with benznidazole therapy, one of which was accompanied by jaundice. Furthermore, cases of immunoallergic hepatitis have been reported with other more commonly used nitroimidazoles such as metronidazole and ornidazole, some of which have been severe. Thus, benznidazole therapy has had limited clinical use, but it appears to have the potential to cause symptomatic, immunoallergic hepatitis with jaundice.
Likelihood score: D (possible rare cause of clinically apparent liver injury, usually as a component of DRESS syndrome).

---

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Benznidazole is excreted into milk in dosages much lower than the treatment dosage for infants. Because of the low levels of benznidazole in breastmilk and safety when given directly to infants, its use is acceptable in nursing mothers.
◉ Effects in Breastfed Infants
Ten women with chronic Chagas disease received benznidazole in a median oral dose of 5.65 mg/kg twice daily for 30 days. Median infant age Ten women with chronic Chagas disease received benznidazole in a median oral dose of 5.65 mg/kg twice daily for 30 days. Median infant age was 5.2 months (range 20 days-13 months). Five children were exclusively breastfed and the others partially breastfed. None of the infants had any adverse reactions attributable to benznidazole.
A postpartum woman diagnosed with Chagas disease was treated with benznidazole 5 mg/kg daily beginning one month postpartum and continuing for 30 days. She continued to breastfeed (extent not stated) her infant. The authors reported that no adverse effects were seen in the infant.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

[1]. Int J Antimicrob Agents. 2007 Jun;29(6):733-7.

[2]. Biomedica. 2009 Sep;29(3):448-55.

[3]. PLoS Negl Trop Dis.2018 Nov 1;12(11):e0006814.

Benznidazole is a monocarboxylic acid amide obtained by formal condensation of the carboxy group of (2-nitroimidazol-1-yl)acetic acid with the aromatic amino group of benzylamine. Used for treatment of Chagas disease. It has a role as an antiprotozoal drug. It is a member of imidazoles, a C-nitro compound and a monocarboxylic acid amide.
Benznidazole is an antiprotozoal prescription medicine approved by the Food and Drug Administration (FDA) for the treatment of Chagas disease caused by infection with the parasite Trypanosoma cruzi. Benznidazole is FDA-approved for use in children 2 to 12 years of age.
Chagas disease can be opportunistic infections (OI) of HIV.
Benznidazole was granted accelerated approval for the treatment of Chagas disease in children 2-12 years of age by the FDA on August 29, 2017. It is the first treatment made available in the United States for Chagas disease.
Benznidazole is an orally available, broad spectrum antimicrobial agent used in the treatment of Chagas disease (American trypanosomiasis). Benznidazole is a nitroimidazole similar to metronidazole and is associated with serum enzyme elevations during therapy in up to 10% of patients but has not linked to cases of clinically apparent acute liver injury.
Benznidazole has been reported in Xenorhabdus nematophila with data available.
Benznidazole is a nitroimidazole derivative having an antiprotozoal activity by interfering with parasite protein biosynthesis, influencing cytokines production and stimulating host phagocytosis. (NCI)

---

Drug Indication
For use in the treatment of Chagas disease in children 2-12 years of age.

---

Mechanism of Action
Benznidazole is thought to be reduced to various electrophilic metabolites by nitroreductases present in *Trypanosoma cruzi*. These metabolites likely bind to proteins, lipids, DNA, and RNA resulting in damage to these macromolecules. Benznidazole has been found to increase trypanosomal death through interferon-γ which is likely present in increased amounts due to inflammation caused by macromolecule damage. DNA in parasites affected by benznidazole has been found to undergo extensive unpacking with overexpression of DNA repair proteins supporting the idea of DNA damage contributing to the mechanism of the drug.

---

Pharmacodynamics
Benznidazole is a trypanocidal agent which kills the causative organism in Chagas disease, *Trypanosoma cruzi*.

C12H12N4O3

260.25

260.091

C, 55.38; H, 4.65; N, 21.53; O, 18.44

22994-85-0

31593

Off-white to light yellow solid powder

1.35g/cm3

189-192ºC(lit.)

1.643

2.021

92.74

1

4

4

19

325

0

O=C(C([H])([H])N1C([H])=C([H])N=C1[N+](=O)[O-])N([H])C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H]

CULUWZNBISUWAS-UHFFFAOYSA-N

InChI=1S/C12H12N4O3/c17-11(14-8-10-4-2-1-3-5-10)9-15-7-6-13-12(15)16(18)19/h1-7H,8-9H2,(H,14,17)

2-Nitro-N-(phenylmethyl)-1H-imidazole-1-acetamide

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)

DMSO : 50~52 mg/mL ( 192.12~199.8 mM )
Ethanol : ~5 mg/mL

配方 1 中的溶解度: ≥ 2.08 mg/mL (7.99 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 20.8 mg/mL澄清DMSO储备液加入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。

---

配方 2 中的溶解度: ≥ 2.08 mg/mL (7.99 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 20.8 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。

---

View More

配方 3 中的溶解度: ≥ 2.08 mg/mL (7.99 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 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

---

配方 4 中的溶解度: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.08 mg/mL (7.99 mM)

---

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。