Absorption, Distribution and Excretion
Rapidly absorbed and peak plasma concentration is reached within 1 to 2 hours after the oral administration of a suspension. Some systemic absorption may occur from topical preparations applied to the skin.
It is metabolized almost completely to the 5-hydroxy form which appears in the urine as glucuronide or sulfate conjugates.
Investigations in mice, rats and dogs using (14)C-labelled thiabendazole indicated that oral doses were rapidly absorbed from the gut and were distributed throughout the body (including the brain). Only 0.01% of the (14)C-thiabendazole given to rats was recovered as (14)C-carbon dioxide. Thiabendazole readily crossed the placental barrier to expose the fetuses.
It becomes distributed throughout most of the body tissues, its highest concn in blood occurring at 4-7 hr after admin /in animals/.
Absorption of thiabendazole by parasites is probably through the cuticle. Evidence from in vitro studies ... suggests that absorption ... is by means of passive diffusion of molecule through lipid barrier of nematode cuticle. This ... is not necessarily the case in vivo.
Thiabendazole is rapidly absorbed and peak plasma concentrations occur within 1 to 2 hours. It is metabolized almost completely and appears in the urine as conjugates. In 48 hours, approximately 5% of the administered dose is recovered from feces and approximately 90% from urine. Most is excreted within the first 24 hours.
For more Absorption, Distribution and Excretion (Complete) data for THIABENDAZOLE (10 total), please visit the HSDB record page.

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Metabolism / Metabolites
Hepatic. Metabolized almost completely to the 5-hydroxy form which appears in the urine as glucuronide or sulfate conjugates.
In mice, rats and humans, the main pathway of metabolism of thiabendazole is an initial hydroxylation to form 5-hydroxythiabendazole, followed by conjugation to 5-hydroxythiabendazole glucuronide and 5-hydroxythiabendazole sulfate. In rats, 4-hydroxythiabendazole and 2-acetylbenzimidazole have been identified as minor metabolites or degradation products in urine.
... Treated beet leaves were exposed to sunlight for equiv of 14 8-hr days ... in addn to benzimidazole-2-carboxamide, benzimidazole and polar and polymer products were formed ... Thiabendazole was not metabolized by potatoes or cotton ...
A single oral dose of thiabendazole was administered to four male human subjects. Feces and urine were collected. After an oral dose of 1.0 g of (14)C thiabendazole, plasma levels peaked at 1 to 2 hr and large amounts of radioactivity appeared rapidly in the urine. More than 40% of the label was excreted within 4 hr and 80% in 24 hr. Most of the dose appeared in urine as the glucuronide (35%) and sulfate (13%) of 5-hydroxy-TBZ. A small amount of unchanged TBZ and unconjugated 5-HO-TBZ were also present. The same compounds were observed with rats and dogs. It has also been reported that (14)C-labeling of the benzene ring in thiabendazole gave rise to some (14)CO2 by rats, indicating ring cleavage.
Rat hepatic mixed function oxidase /activities in microsomal/ preparations hydroxylated thiabendazole. This activity seemed to be greatest in microsomal preparations > hepatocytes > slices.
For more Metabolism/Metabolites (Complete) data for THIABENDAZOLE (9 total), please visit the HSDB record page.
Thiabendazole has known human metabolites that include 5-hydroxythiabendazole.
Hepatic. Metabolized almost completely to the 5-hydroxy form which appears in the urine as glucuronide or sulfate conjugates.
Route of Elimination: It is metabolized almost completely to the 5-hydroxy form which appears in the urine as glucuronide or sulfate conjugates.
Half Life: The half-life for thiabendazole in both normal and anephric patients is 1.2 hours (range 0.9 to 2 hours). The half-life for the 5-hydroxythiabendazole metabolite in both normal and anephric patients is 1.7 hours (range 1.4 to 2 hours).

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Biological Half-Life
The half-life for thiabendazole in both normal and anephric patients is 1.2 hours (range 0.9 to 2 hours). The half-life for the 5-hydroxythiabendazole metabolite in both normal and anephric patients is 1.7 hours (range 1.4 to 2 hours).

Toxicity Summary
The precise mode of action of thiabendazole on the parasite is unknown, but it most likely inhibits the helminth-specific enzyme fumarate reductase.

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Hepatotoxicity
Thiabendazole therapy is associated with serum aminotransferase elevations in up to 36% of patients, but it is usually given for a brief period only and its effects on serum enzyme levels after single dose administration has not been systematically evaluated. Importantly, thiabendazole therapy has also been associated with clinically apparent liver injury which can be prolonged and severe. The onset of injury is usually within 1 to 2 weeks of finishing a 1 to 5 day course of therapy. The pattern of serum enzyme elevations is typically cholestatic. Autoantibodies are usually negative and fever, arthralgias and rash are uncommon. Several reported cases have been associated with sicca complex marked by parotid enlargement and tenderness, dry eyes and dry mouth arising before the onset of jaundice (Case 1). The cholestatic injury can be associated with damage to small bile ducts and with prolonged jaundice and/or pruritus and alkaline phosphatase elevations. Several instances of prolonged cholestasis and chronic vanishing bile duct syndrome and end stage liver disease has been reported even after a single dose of thiabendazole.

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Toxicity Data
The oral LD 50 is 3.6 g/kg, 3.1 g/kg and 3.8 g/kg in the mouse, rat, and rabbit respectively.

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Interactions
Thiabendazole had no protective effects against pentylenetetrazole-induced convulsions in rats at 20-100 mg/kg, whereas 200 mg/kg sc incr frequency of clonic convulstions resulting in 100% mortality.
Strongyloidiasis in immunosuppressed pt often requires prolonged admin of the anthelmintic, thiabendazole. The case described herein represents the first report of theophylline toxicity induced by concurrent admin of thiabendazole. Preliminary studies suggest that interference with theophylline clearance by thiabendazole may be the mechanism in this drug interaction.
Thiabendazole may compete with other drugs (eg, theophylline) for sites of metabolism in the liver and thereby increase serum concentrations of such drugs to potentially toxic levels. When thiabendazole and a xanthine derivative are used concomitantly, it may be necessary to monitor serum concentrations of the xanthine derivative and/or reduce its dosage. Patients receiving the drugs concomitantly should be carefully monitored.
A probable drug interaction between theophylline and thiabendazole is reported in a 49-yr-old asthmatic male patient initially receiving 300 mg of oral sustained-action theophylline anhydrous 2 times/day, who was given oral thiabendazole suspension at a dose of 1.8 g 2 times/day (total of 6 doses) for the treatment of strongyloidiasis. The patient's serum theophylline concentration was 14 ug/mL before thiabendazole therapy. The dosage of Theo-Dur was decreased to 200 mg twice daily; however, serum theophylline concentrations increased to 22 ug/mL. The dose was then decreased to 150 mg 2 times/day, resulting in serum theophylline levels of 12 ug/mL. Before initiation of thiabendazole therapy, the patient's estimated baseline theophylline clearance was about 1.7 L/hr; after thiabendazole therapy was begun, this clearance fell to about 0.8 L/hr. Nine days after cessation of thiabendazole therapy, theophylline clearance was close to the baseline value. It was concluded that in patients on theophylline therapy, a 50% reduction in theophylline dosage should be considered when thiabendazole therapy is initiated.

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Non-Human Toxicity Values
LD50 Mouse oral 3.6 g/kg
LD50 Rat oral 3.1 g/kg
LD50 Rabbit oral 3.85 g/kg
LD50 Rat oral 2080 mg/kg
For more Non-Human Toxicity Values (Complete) data for THIABENDAZOLE (10 total), please visit the HSDB record page.

[1]. Review of Characteristics and Analytical Methods for Determination of Thiabendazole. Molecules. 2023 May 6;28(9):3926.

[2]. Thiabendazole, a well-known antifungal drug, exhibits anti-metastatic melanoma B16F10 activity via inhibiting VEGF expression and inducing apoptosis. Pharmazie, 2013. 68(12): p. 962-8.

[3]. Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent. PLoS Biol, 2012. 10(8): p. e1001379.

[4]. Developmental defects induced by thiabendazole are mediated via apoptosis, oxidative stress and alteration in PI3K/Akt and MAPK pathways in zebrafish. Environ Int. 2023 Jun;176:107973.

[5]. Thiabendazole-induced suppression of renal damage in a murine model of autoimmune disease. Am J Pathol. 1984 May;115(2):204-11.

[6]. Modulation of immune functions, inflammatory response, and cytokine production following long-term oral exposure to three food additives; thiabendazole, monosodium glutamate, and brilliant blue in rats. Int Immunopharmacol. 2021 Sep;98:107902.

Thiabendazole appears as white or cream-colored odorless, tasteless powder. Sublimes above 590 °F. Fluoresces in acidic solution. Formulated as a dust, flowable powder or wettable powder for use as a systemic fungicide and anthelmintic.
Thiabendazole is a member of the class of benzimidazoles carrying a 1,3-thiazol-4-yl substituent at position 2. A mainly post-harvest fungicide used to control a wide range of diseases including Aspergillus, Botrytis, Cladosporium and Fusarium. It has a role as an antifungal agrochemical and an antinematodal drug. It is a member of benzimidazoles, a member of 1,3-thiazoles and a benzimidazole fungicide. It derives from a hydride of a 1H-benzimidazole.
2-Substituted benzimidazole first introduced in 1962. It is active against a variety of nematodes and is the drug of choice for strongyloidiasis. It has CNS side effects and hepatototoxic potential. (From Smith and Reynard, Textbook of Pharmacology, 1992, p919)
Thiabendazole is an Anthelmintic.
Thiabendazole is a broad spectrum anthelmintic agent used predominantly in treatment of intestinal pinworm and strongyloides infection, which recently has been replaced by better tolerated agents. Thiabendazole therapy has been shown to cause clinically apparent cholestatic liver injury which is rare, but can be severe.
Thiabendazole is a benzimidazole derivative with anthelminthic property. Although the mechanism of action has not been fully elucidated, thiabendazole inhibits the helminth-specific mitochondrial enzyme fumarate reductase, thereby inhibiting the citric acid cycle, mitochondrial respiration and subsequent production of ATP, ultimately leading to helminth's death. In addition, it has been suggested that thiabendazole may lead to inhibition of microtubule polymerization by binding to beta-tubulin and has an overt ovicidal effect with regard to some trichostrongylids.
Thiabendazole is a fungicide and parasiticide. It is used primarily to control mold, blight, and other fungally caused diseases in fruits (e.g. oranges) and vegetables; it is also used as a prophylactic treatment for Dutch elm disease. As an antiparasitic, it is able to control roundworms (such as those causing strongyloidiasis), hookworms, and other helminth species which attack wild animals, livestock and humans.
2-Substituted benzimidazole first introduced in 1962. It is active against a variety of nematodes and is the drug of choice for STRONGYLOIDIASIS. It has CENTRAL NERVOUS SYSTEM side effects and hepatototoxic potential. (From Smith and Reynard, Textbook of Pharmacology, 1992, p919)
See also: Thiabendazole; Trichlorfon (component of); Dexamethasone; Neomycin Sulfate; Thiabendazole (component of).

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Drug Indication
For the treatment of strongyloidiasis (threadworm), cutaneous larva migrans (creeping eruption), visceral larva migrans, and trichinosis.
FDA Label

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Mechanism of Action
The precise mode of action of thiabendazole on the parasite is unknown, but it most likely inhibits the helminth-specific enzyme fumarate reductase.
Thiabendazole and other benzimidazole anthelmintics act by binding strongly to tubulin in the absorptive cells in the gut of parasitic worms. This interferes with the uptake of nutrients and the worms effectively starve to death. The host is less affected as the binding to mammalian tubulin is less strong and is reversible.
Although the exact mechanism of anthelmintic activity of thiabendazole has not been fully elucidated, the drug has been shown to inhibit the helminth-specific enzyme, fumarate reductase. In animals, thiabendazole has anti-inflammatory, antipyretic, and analgesic effects.

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Therapeutic Uses
Antinematodal Agents
MEDICATION (VET): Thiabendazole is included in some otic preparations for treatment of yeast infections.
MEDICATION (VET): The antifungal imidazoles also have some antibacterial action but are rarely used for this purpose. ... Thiabendazole is effective against Aspergillus and Penicillium spp , but its use has largely been replaced by the more effective imidazoles.
MEDICATION (VET): Imidazoles may have antibacterial, antifungal, antiprotozoal, and anthelmintic activity. ... The anthelmintic thiabendazole is also an imidazole with antifungal properties.
For more Therapeutic Uses (Complete) data for THIABENDAZOLE (10 total), please visit the HSDB record page.

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Drug Warnings
The clinical utility of thiabendazole in adults is compromised by its toxicity. Side effects frequently encountered with therapeutic doses include anorexia, nausea, vomiting, and dizziness. Less frequently, diarrhea, fatigue, drowsiness, giddiness, or headache occur. Occasional fever, rashes, erythema multiforme, hallucinations, sensory disturbances, and Stevens-Johnson syndrome have been reported. Angioedema, shock, tinnitus, convulsions, and intrahepatic cholestasis are rare complications of therapy. Some patients excrete a metabolite that imparts an odor to the urine much like that occurring after ingestion of asparagus. Crystalluria without hematuria has been reported on occasion; it promptly subsides with discontinuation of therapy. Transient leukopenia has been noted in a few patients on thiabendazole therapy. There are no absolute contraindications to the use of thiabendazole. Because CNS side effects occur frequently, activities requiring mental alertness should be avoided during therapy. Thiabendazole has hepatotoxic potential and should be used with caution in patients with hepatic disease or decreased hepatic function.
Hypersensitivity reactions consisting of pruritus, fever, facial flush, chills, conjunctival injection, rash (including perianal), angioedema, anaphylaxis, erythema multiforme (including Stevens-Johnson syndrome with some fatalities), and lymphadenopathy have occurred.
Because adverse CNS effects of thiabendazole may occur quite frequently, patients should be warned that the drug may impair their ability to perform activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle) and that such activities should be avoided.
Thiabendazole should be used with caution in patients in whom vomiting might be dangerous and in patients with severe malnutrition or anemia. Ideally, supportive therapy is indicated for anemic, dehydrated, or malnourished patients prior to administration of the drug.
For more Drug Warnings (Complete) data for THIABENDAZOLE (19 total), please visit the HSDB record page.

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Pharmacodynamics
Thiabendazole is a fungicide and parasiticide. Thiabendazole is also a chelating agent, which means that it is used medicinally to bind metals in cases of metal poisoning, such as lead poisoning, mercury poisoning or antimony poisoning. Thiabendazole is vermicidal and/or vermifugal against Ascaris lumbricoides ("common roundworm"), Strongyloides stercoralis (threadworm), Necator americanus, Ancylostoma duodenale (hookworm), Trichuris trichiura (whipworm), Ancylostoma braziliense (dog and cat hookworm), Toxocara canis, Toxocara cati (ascarids), and Enterobius vermicularis (pinworm). Thiabendazole also suppresses egg and/or larval production and may inhibit the subsequent development of those eggs or larvae which are passed in the feces.

C10H7N3S

201.247

201.036

148-79-8

Thiabendazole-d4;1190007-20-5;Thiabendazole-13C6;2140327-29-1

5430

White to off-white solid powder

1.4±0.1 g/cm3

446.0±37.0 °C at 760 mmHg

298-301ºC

226.2±16.9 °C

0.0±1.1 mmHg at 25°C

1.740

2.47

69.81

1

3

1

14

212

0

WJCNZQLZVWNLKY-UHFFFAOYSA-N

InChI=1S/C10H7N3S/c1-2-4-8-7(3-1)12-10(13-8)9-5-14-6-11-9/h1-6H,(H,12,13)

4-(1H-benzimidazol-2-yl)-1,3-thiazole

Thiabendazol; Thibendole; TBZ

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 mg/mL (~248.45 mM)
H2O : ~0.1 mg/mL (~0.50 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (12.42 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 (12.42 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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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。