Absorption, Distribution and Excretion
Following oral administration, the drug is rapidly absorbed, reaching peak plasma concentrations within 1–2 hours. Topical formulations may be partially absorbed. The drug is almost completely metabolized to its 5-hydroxy form and excreted in the urine as glucuronide or sulfate conjugates. Studies using 14C-labeled thiabendazole in mice, rats, and dogs have shown that oral doses are rapidly absorbed from the intestine and distributed throughout the body, including the brain. Only 0.01% of 14C-labeled thiabendazole administered to rats was recovered as 14C-labeled carbon dioxide. Thiabendazole readily crosses the placental barrier, exposing the fetus to the drug. It is distributed throughout most body tissues, reaching peak plasma concentrations 4–7 hours after administration to animals. Parasitic absorption of thiabendazole may occur via the epidermis. In vitro studies suggest that absorption occurs via passive molecular diffusion across the lipid barrier of the nematode epidermis. However, this may not be the case in vivo. Thiabendazole is rapidly absorbed, with peak plasma concentrations occurring within 1–2 hours. It is almost completely metabolized, appearing in the urine as conjugates. Within 48 hours, approximately 5% of the administered dose is recovered in feces, and approximately 90% in urine. Most of the drug is excreted within 24 hours. For more complete data on the absorption, distribution, and excretion of thiabendazoles (10 in total), please visit the HSDB record page. Metabolism/Metabolites: Hepatic metabolism. Almost completely metabolized to the 5-hydroxy form, appearing in the urine as glucuronide or sulfate conjugates. In mice, rats, and humans, the main metabolic pathway of thiabendazole involves initial hydroxylation to form 5-hydroxythiabendazole, followed by conjugation to form 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 exposed to sunlight for the equivalent of 14 eight-hour days...beneficials, in addition to benzimidazole-2-carboxamide, also produce benzimidazole and polar polymer products...thiabendazole is not metabolized by potatoes or cotton... Four male subjects received a single oral dose of thiabendazole. Feces and urine were collected. Following oral administration of 1.0 g of 14C-labeled thiabendazole, peak plasma concentrations were reached within 1 to 2 hours, and large amounts of radioactive material rapidly appeared in the urine. Over 40% of the labeled material was excreted within 4 hours, and 80% within 24 hours. The majority of the dose appeared in the urine as 5-hydroxythiabendazole glucuronide (35%) and sulfate (13%). Small amounts of unaltered thiabendazole (TBZ) and unbound 5-hydroxythiabendazole (5-HO-TBZ) were also present. The same compound was also observed in rats and dogs. It has been reported that the (14)C labeling on the thiabendazole benzene ring produced some (14)CO2 in rats, indicating ring cleavage.
Active activity of hydroxylated thiabendazole in rat liver mixed-function oxidases/microsomes/preparations. This activity appears to be highest in microsomal preparations, followed by hepatocytes, and lastly liver sections.
For more complete data on the metabolism/metabolites of thiabendazole (9 in total), please visit the HSDB record page.
Known human metabolites of thiabendazole include 5-hydroxythiabendazole.
Hepatitis. Almost completely metabolized to the 5-hydroxy form, appearing in urine as glucuronide or sulfate conjugates.
Elimination pathway: Almost completely metabolized to the 5-hydroxy form, appearing in urine as glucuronide or sulfate conjugates.
Half-life: The half-life of thiabendazole in both healthy individuals and patients without kidneys is 1.2 hours (range 0.9 to 2 hours). The half-life of the 5-hydroxythiabendazole metabolite in both healthy individuals and patients without kidneys is 1.7 hours (range 1.4 to 2 hours).

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Biological half-life
The half-life of thiabendazole in both healthy individuals and patients without kidneys is 1.2 hours (range 0.9 to 2 hours). The half-life of the 5-hydroxythiabendazole metabolite in both healthy individuals and patients without kidneys is 1.7 hours (range 1.4 to 2 hours).

Toxicity Summary
The exact mechanism of action of thiabendazole against parasites is unclear, but it is most likely due to inhibition of the worm-specific enzyme fumarate reductase. Hepatotoxicity
Thiabendazole treatment is associated with elevated serum transaminases in up to 36% of patients, but it is usually administered only for short periods, and the effect of a single dose on serum enzyme levels has not been systematically evaluated. Importantly, thiabendazole treatment is also associated with clinically significant liver injury, which can be prolonged and severe. Injury typically occurs within 1 to 2 weeks after completion of a 1 to 5-day course of treatment. The pattern of elevated serum enzymes is usually cholestatic. Autoantibodies are usually negative, and fever, arthralgia, and rash are uncommon. Several cases have been reported in association with Sjögren's syndrome, characterized by parotid gland swelling and tenderness, dry eyes, and dry mouth, which precede the onset of jaundice (Case 1). Cholestatic injury may be associated with small bile duct damage, prolonged jaundice duration, and/or pruritus and elevated alkaline phosphatase. Even single doses of thiabendazole have been reported to cause persistent cholestasis, chronic disappearance of bile duct syndrome, and end-stage liver disease. Toxicity Data: The oral LD50 of thiabendazole in mice, rats, and rabbits is 3.6 g/kg, 3.1 g/kg, and 3.8 g/kg, respectively. Interactions: Thiabendazole at doses of 20–100 mg/kg has no protective effect against pentylenetetrazol-induced seizures in rats, while subcutaneous injection at 200 mg/kg increases the frequency of clonic seizures, leading to 100% mortality. Strongyloides stercoralis infection in immunosuppressed patients often requires long-term use of the anthelmintic thiabendazole. The case described in this article is the first reported case of theophylline poisoning due to concurrent use of thiabendazole. Preliminary studies suggest that thiabendazole's interference with theophylline clearance may be the mechanism leading to this drug interaction.
Tiabendazole may compete with other drugs (such as theophylline) for hepatic metabolic sites, potentially leading to elevated serum concentrations of these drugs at potentially toxic levels. When thiabendazole is used concomitantly with xanthine derivatives, monitoring of serum xanthine derivative concentrations and/or dose reduction may be necessary. Patients taking both drugs concurrently should be closely monitored.
A 49-year-old male patient with asthma has been reported to have a possible drug interaction between theophylline and thiabendazole. The patient initially received oral extended-release anhydrous theophylline 300 mg twice daily, followed by oral thiabendazole suspension at a dose of 1.8 g twice daily (for a total of 6 doses) for treatment of strongyloidosis stercoralis. Before receiving thiabendazole treatment, the patient's serum theophylline concentration was 14 μg/mL. The dose of thiabendazole extended-release tablets (Theo-Dur) was reduced to 200 mg twice daily; however, the serum theophylline concentration increased to 22 μg/mL. Subsequently, the dose was again reduced to 150 mg twice daily, and the serum theophylline concentration decreased to 12 μg/mL. Before initiating thiabendazole treatment, the patient's baseline theophylline clearance was estimated at approximately 1.7 L/hr; after initiation of thiabendazole treatment, this clearance decreased to approximately 0.8 L/hr. Nine days after discontinuation of thiabendazole, theophylline clearance returned to near baseline. The conclusion is that for patients receiving theophylline treatment, a 50% reduction in theophylline dose should be considered when initiating thiabendazole treatment.

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Non-human toxicity values
Mice oral LD50 3.6 g/kg
Rats oral LD50 3.1 g/kg
Rabbit oral LD50 3.85 g/kg
Rats oral LD50 2080 mg/kg
For more complete non-human toxicity data for thiabendazole (out of 10), 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 is a white or off-white, odorless and tasteless powder. It sublimes above 590°F. It fluoresces in acidic solutions. It is formulated as a powder, flowable powder, or wettable powder and used as a systemic fungicide and insecticide. Thiabendazole belongs to the benzimidazole class of compounds, with a 1,3-thiazol-4-yl substituent at the 2 position. It is mainly used for postharvest fungicide control of various diseases, including aspergillosis, gray mold, cladoceranosis, and Fusarium infection. It is both an antifungal pesticide and an antinematode. It is a benzimidazole compound, a 1,3-thiazazole compound, and a benzimidazole fungicide. It is derived from the hydride of 1H-benzimidazole. 2-Substituted benzimidazole was first introduced in 1962. It is effective against various nematodes and is the first-line drug for treating strongyloidiasis. It has central nervous system side effects and hepatotoxicity. (Excerpted from Smith and Reynard, Pharmacology Textbook, 1992, p. 919)
Thiabendazole is an anthelmintic.
Thiabendazole is a broad-spectrum anthelmintic, primarily used to treat intestinal pinworm and strongyloides stercoralis infections, but it has been largely replaced in recent years by better-tolerated drugs. Thiabendazole treatment has been shown to cause clinically significant cholestatic liver injury, which, although rare, can be severe.
Thiabendazole is a benzimidazole derivative with anthelmintic properties. Although its mechanism of action is not fully elucidated, thiabendazole inhibits the worm-specific mitochondrial enzyme fumarate reductase, thereby inhibiting the citrate cycle, mitochondrial respiration, and subsequent ATP production, ultimately leading to worm death. Furthermore, studies have shown that thiabendazole may inhibit microtubule polymerization by binding to β-tubulin and has significant ovicidal activity against certain strongyloides worms. Thiabendazole is also a bactericide and antiparasitic agent. It is mainly used to control mold, wilt, and other fungal diseases in fruits (such as oranges) and vegetables; it can also be used as a preventative treatment for Dutch elm disease. As an antiparasitic drug, it can control roundworms (such as the roundworm that causes strongyloidiasis), hookworms, and other worms that infest wild animals, livestock, and humans. 2-Substituted benzimidazole was first introduced in 1962. It is effective against a variety of nematodes and is the drug of choice for treating strongyloidiasis. It has central nervous system side effects and hepatotoxicity. (Quoted from Smith and Reynard, Pharmacology Textbook, 1992, p. 919) See also: thiabendazole; trichlorfon (component); dexamethasone; neomycin sulfate; thiabendazole (component).

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Drug Indications
Used to treat strongyloidiasis (nematode disease), cutaneous larval migration (creeping rash), visceral larval migration, and trichinosis.

FDA Label
>Mechanism of Action>
The exact mechanism of action of thiabendazole on parasites is not fully understood, but it likely inhibits the worm-specific enzyme fumarate reductase.
Thiabendazole and other benzimidazole anthelmintics work by strongly binding to tubulin in the absorptive cells of the parasite's intestines. This interferes with nutrient absorption, leading to the worm's eventual starvation. Because thiabendazole's binding to mammalian tubulin is weak and reversible, its impact on the host is minimal.
Although the anthelmintic mechanism of thiabendazole is not fully elucidated, it has been shown to inhibit the worm-specific enzyme fumarate reductase. In animals, thiabendazole has anti-inflammatory, antipyretic, and analgesic effects.
Therapeutic Uses>
Antinematode Drugs
Veterinary Use: Thiabendazole is an ingredient in some ear preparations used to treat yeast infections.
Veterinary Use: Imidazole antifungal drugs also have some antibacterial activity, but are rarely used for this purpose. Thiabendazole is effective against Aspergillus and Penicillium fungi, but its use has been superseded by more effective imidazole drugs.
Drugs (Veterinary): Imidazole drugs may have antibacterial, antifungal, antiseptic, and anthelmintic activities. ...The anthelmintic thiabendazole is also an imidazole drug with antifungal properties.
For more complete data on the therapeutic uses of thiabendazole (10 in total), please visit the HSDB record page.

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Drug Warnings
The clinical use of thiabendazole in adults is limited due to its toxicity. Common side effects at therapeutic doses include anorexia, nausea, vomiting, and dizziness. Less common side effects include diarrhea, fatigue, drowsiness, dizziness, or headache.Occasional fever, rash, erythema multiforme, hallucinations, sensory disturbances, and Stevens-Johnson syndrome have been reported. Angioedema, shock, tinnitus, seizures, and intrahepatic cholestasis are rare treatment complications. Some patients may excrete a metabolite that gives their urine an odor similar to that of asparagus. Crystalluria without hematuria has been occasionally reported; this usually resolves rapidly upon discontinuation of the drug. A small number of patients treated with thiabendazole have experienced transient leukopenia. There are no absolute contraindications to thiabendazole. Due to the high incidence of central nervous system side effects, activities requiring mental concentration should be avoided during treatment. Thiabendazole is hepatotoxic; it should be used with caution in patients with liver disease or impaired liver function. Hypersensitivity reactions have been reported, including itching, fever, facial flushing, chills, conjunctival congestion, rash (including perianal rash), angioedema, anaphylactic shock, erythema multiforme (including Stevens-Johnson syndrome, with some fatalities), and lymphadenopathy. Because of the high incidence of central nervous system adverse reactions to thiabendazole, patients should be informed that the drug may impair their ability to perform activities requiring mental alertness or physical coordination (such as operating machinery or driving motor vehicles), and advised to avoid such activities.
Tibendazole should be used with caution in patients whose vomiting may be life-threatening, as well as in patients with severe malnutrition or anemia. Ideally, supportive care should be provided to patients with anemia, dehydration, or malnutrition before administering this medication.
For more complete data on thiabendazole (19 in total), please visit the HSDB records page.

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Pharmacodynamics
Tibendazole is a fungicide and antiparasitic agent. It is also a chelating agent, meaning it is used medically to chelate metals to treat metal poisoning such as lead, mercury, or antimony poisoning. Thiabendazole has anthelmintic and/or anthelmintic effects against Ascaris lumbricoides, Strongyloides stercoralis, Necator americanus, Ancylostoma duodenale, Trichuris trichiura, Ancylostoma braziliense, Toxocara canis, Toxocara cati, and Enterobius vermicularis. Thiabendazole can also inhibit the production of eggs and/or larvae, and may inhibit the subsequent development of eggs or larvae excreted in 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

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (12.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)