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At least 19 recordsLinked to original sources
PubMed1987

HPLC determination and pharmacokinetics of thiabendazole and its major metabolite 5-OH thiabendazole in equine plasma.

Separate high performance liquid chromatographic methods were developed for thiabendazole (TBZ) and 5-hydroxy thiabendazole (5-OH-TBZ) determination in horse plasma using 1-methyl-2-phenyl benzimidazole (MPBZ) as an internal standard. In both methods TBZ and 5-OH-TBZ were extracted from plasma using organic solvents, injected on to a C-18 column, and eluents monitored by a fluorescence detector. However, mobile phase composition, extraction solvent as well as detector wavelength differed in the two methods. The linear range for TBZ was 0.02 to 0.77 microgram ml-1 while that for 5-OH-TBZ was 0.96 to 8.0 micrograms ml-1. A commercially available TBZ oral suspension was administered to four thoroughbred horses in the following manner: days 1 and 2, 44 mg kg-1; days 4 and 5, 440 mg kg-1. Blood samples were collected during the 24 hours after administration and then analysed for TBZ and 5-OH-TBZ. Half-lives (t1/2), maximum plasma concentrations (Cmax), area under plasma concentration time curves (AUC O-alpha), and relative apparent bioavailability (F), were determined using pharmacokinetic equations. The pharmacokinetic parameters varied in the following manner: 1.16 to 13.63 hours (t1/2), 12 to 131 micrograms ml-1 X hours (AUC O-alpha), 3.33 to 8.90 micrograms ml-1 (Cmax), 1.38 to 0.12 (F) after 44 mg kg-1 and 440 mg kg-1 doses, respectively. The ratios of concentrations of TBZ to 5-OH-TBZ after oral administration of TBZ, were significantly lower for 44 mg kg-1 than 440 mg kg-1 doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

New metabolites of thiabendazole and the metabolism of thiabendazole by mouse embryo in vivo and in vitro.

Thiabendazole [2-(4'-thiazolyl)benzimidazole; TBZ], a teratogen in ICR mice, is known to be mainly metabolized to 5-hydroxy-TBZ (5-OH-TBZ) and its conjugates in domestic and laboratory animals. Besides the known metabolites of TBZ, 4-hydroxy-TBZ and 2-acetylbenzimidazole (ABI) were identified as new metabolites of TBZ in the urine of F344 rats and ICR mice. 5-OH-TBZ and ABI, as well as TBZ, were found in the embryos of ICR mice given TBZ orally on day 10 of gestation. In the whole-embryo culture system, 5-OH-TBZ and ABI in the medium, and TBZ, 5-OH-TBZ and ABI in the embryo were detected after 24 hr of culture in 25 or 50 micrograms TBZ ml. However, the amount of metabolites in the embryo in vitro was very small compared with that detected in vivo, whereas the amount of TBZ was comparable. Furthermore, the mouse embryo homogenate, at organogenesis, metabolized TBZ to 5-OH-TBZ or ABI. The specific activity required by this homogenate to form 5-OH-TBZ or ABI was less than 1/1000 of that of the liver microsomal fraction. The results suggested that mouse embryos at organogenesis could metabolize TBZ, although most of the metabolites in the embryo in vivo came from the dam.

Animals↗
PubMed2004

Synthesis, antimicrobial activity and chemotherapeutic potential of inorganic derivatives of 2-(4'-thiazolyl)benzimidazole[thiabendazole]: X-ray crystal structures of [Cu(TBZH)2Cl]Cl.H2O.EtOH and TBZH2NO3 (TBZH=thiabendazole).

Thiabendazole (TBZH) reacts with iron(III) nitrate causing protonation of the ligand to yield the nitrate salt [TBZH(2)NO(3)] (1). Reaction of TBZH with copper(II) acetate results in the deprotonation of the ligand yielding [Cu(TBZ)2.(H2O)2] (2). Reactions of TBZH with the chloride, nitrate and butanedioate salts of copper(II) yields [Cu(TBZH)2Cl]Cl.H2O.EtOH (3), [Cu(TBZH)(2)(NO(3))(2)] (4) and [Cu(TBZH)(O(2)C-CH(2)CH(2)-CO(2))] (5), respectively. The TBZH acts as a neutral chelating ligand in 3-5. Molecular structures of 1 and 3 were determined crystallographically. In 1, the asymmetric unit contains one TBZH(2)(+) cation and one NO(3)(-) anion. The structure of 3 comprises a five coordinate copper centre with the metal bound to two chelating TBZH ligands and one chloride. The geometry is best described as trigonal bipyramidal. Hydrogen bonding connects the complex cation with the uncoordinated chloride anion and the water and ethanol solvate molecules. Compound 1 and the copper complexes 2-5, the metal free ligands and a number of simple copper(II) salts were each tested for their ability to inhibit the growth of Candida albicans. The metal free TBZH and its nitrate salt (1) exhibited very poor activity. Complex 2, in which the TBZH is present as an anionic ligand (TBZ(-)), exhibits moderate activity towards the pathogen. Chelation of the neutral TBZH to copper centres (complexes 3-5) results in potent anti-candida activity. The dimethyl sulphoxide (DMSO) soluble complexes 3 and 4, along with metal free TBZH were assessed for their cancer chemotherapeutic potential towards two human epithelial-derived cancer model cell lines. Complexes 3 and 4 displayed similar dose-dependent cytotoxicity in both cell lines with IC(50) values of approximately 50 microM, which were found to be significantly lower than that for metal free TBZH.

Antifungal Agents↗
PubMed1979

The inheritance of thiabendazole resistance in Haemonchus contortus.

Haemonchus contortus worm populations isolated from naturally infected sheep at the Pastoral Research Laboratory, Armidale, N.S.W., were found to contain approximately 20% of worms resistant to a 50 mg/kg dose of thiabendazole. Following 3 generations of selection with 50 mg/kg thiabendazole the number of worms removed by the anthelmintic was too small to detect differences between treated and control groups. After more than 15 generations of selection, matings between males from the selected strain and non-resistant females produced resistant males and females in equal numbers. Thus, thiabendazole resistance does not appear to be sex-linked. A dose--response assay on the F2 adults indicated that worms from female resistant x male non-resistant crosses were more resistant than F2 adults of the reciprocal cross. An in vitro technique that identified thiabendazole-resistant eggs by their ability to hatch in a solution containing thiabendazole and 0.1% NaCl solution was also used to study the inheritance of resistance. F1 eggs had similar LC50's to the resistant parents. F2 and back-cross eggs from an original mating of thiabendazole-resistant females x non-resistant males had a higher LC50 than F2 and back-cross eggs from the reciprocal mating, indicating a degree of matroclinous inheritance of resistance. However, the resistant parents had tolerances to thiabendazole exceeding those of F2. F3 eggs had a resistance distribution that ranged from that of the resistant to the non-resistant parent. No significant deviation from linearity was observed in any of the dose--response lines. These results indicate that thiabendazole resistance in H. contortus worms is inherited as an autosomal and semi-dominant trait.

Animals↗
PubMed1996

Major involvement of rabbit liver cytochrome P4501A in thiabendazole 5-hydroxylation.

1. Thiabendazole is a widely used food preservative and anthelmintic drug for breeding animal species. In order to characterize precisely the cytochrome P450 isozyme(s) involved in its major route of metabolism, a rapid and sensitive spectrofluorimetric method was developed for the simultaneous determination of thiabendazole and its main hepatic metabolite 5-hydroxythiabendazole. 2. The kinetics of thiabendazole 5-hydroxylation were determined in microsomal preparations from control rabbits or animals previously treated with either beta-naphthoflavone, isosafrole, phenobarbital, rifampicin or clofibrate. These treatments led to specific induction of CYP1A1, 1A2, 2B4, 3A6 and 4A1 respectively. 3. By considering this panel of characterised microsomal preparations, only those obtained from BNF-treated rabbits exhibited an increase in thiabendazole 5-hydroxylase activity Ethoxyresorufin O-deethylation in these microsomes was solely inhibited by thiabendazole. These argue for a specific involvement of the CYP1A subfamily. 4. In the CYP1A subfamily, CYP1A2 appears to be responsible for basal 5-hydroxylation and further unidentified metabolism of thiabendazole in control livers. However, the major involvement of CYP1A1 is supported by the following characteristics of 5-hydroxylation of thiabendazole: (1) the correlation with CYP1A1 expression and (2) the inhibition by ellipticine and not by furafylline, inhibitors of CYP1A1 and CYP1A2 respectively. 5. All these data demonstrated that the rabbit cytochrome P4501A is predominantly involved in thiabendazole 5-hydroxylation which has been suspected to be critical in terms of safety of the parent drug.

Animals↗
PubMed1998

Simultaneous determination of thiabendazole and its major metabolite, 5-hydroxythiabendazole, in bovine tissues using gradient liquid chromatography with thermospray and atmospheric pressure chemical ionisation mass spectrometry.

A novel method is presented for the determination of thiabendazole and 5-hydroxythiabendazole in animal tissues. Samples are homogenised in buffer at pH=7.0, extracted with ethyl acetate and cleaned up using CN solid-phase extraction columns. Thiabendazole and 5-hydroxythiabendazole are separated chromatographically using gradient elution and analysed by liquid chromatography-mass spectrometry. Deuterated thiabendazole is employed as an internal standard for thiabendazole determination; 5-hydroxythiabendazole is quantified via external standards. Samples are screened by monitoring the protonated molecular ions at m/z=202 for thiabendazole, 206 for deuterated thiabendazole and 218 for 5-hydroxythiabendazole using thermospray LC-MS. Positives are confirmed by multiple ion monitoring using APCI LC-MS. Validation of the method was carried out at 50, 100 and 200 microg kg(-1). Recoveries for thiabendazole in bovine muscle, liver and kidney ranged from 96-103% with C.V.s between 0.7 and 4.8% and for 5-hydroxythiabendazole recoveries ranged from 70-85% with C.V.s between 3.1 and 11.5%.

Animals↗
PubMed1985

The effect of thiabendazole on pain threshold.

Thiabendazole significantly increased the reaction time to thermal stimulus. However, in mice treated with morphine, the reaction time was not in any way different from those treated with combined doses of thiabendazole and morphine. Thiabendazole was found to have an antinociceptive action. The protective dose for 50% of animal (ED50) against p-benzoquinone-induced writhing reflex was found to be 310 mg/kg. The ED50 for aspirin alone was 140 mg/kg. When the ED50 of aspirin was determined in combination with different dose levels of thiabendazole, it showed a marked reduction in the values reaching 50 mg/kg, when 300 mg of thiabendazole was used in combination. Toxicological studies revealed that the oral LD50 for thiabendazole in mice was 2200 mg/kg, and when combined with 140 mg/kg of aspirin, the LD50 was reduced to 900 mg/kg. These findings indicate that thiabendazole possesses an analgesic activity which is potentiated by aspirin, though aspirin was found to significantly enhance its toxicity.

Analgesics↗
PubMed1979

Inhibition of thiabendazole metabolism in the rat.

1. A single oral dose of desmethylimipramine (80 mg/kg) administered to rats inhibited the hepatic microsomal hydroxylation of thiabendazole (45%), aniline (30%), biphenyl (30%) and ethylmorphine (15%) in vitro at 5 h after dosage; there was no decrease in cytochrome P-450 or b5. 2. A single oral dose of ethoxyquin (200 mg/kg) to rats inhibited the hepatic microsomal hydroxylation of thiabendazole (65%), aniline (40%) and biphenyl (40%) in vitro at 1 h after dosage; inhibition was less at 5 h. There were no changes in the contents of cytochromes P-450 and b5. 3. The max. plasma concn. of thiabendazole occurred 2--4 h after oral dosing (50--200 mg/kg) to rats. Thiabendazole (100 mg/kg) administered orally 30 min after oral ethoxyquin (400 mg/kg) or thiabendazole (200 mg/kg) administered orally 30 min after oral desmethylimipramine (80 mg/kg) delayed absorption of the thiabendazole and resulted in markedly markedly decreased plasma concentration of the anthelmintic. 4. Simultaneous administration of ethoxyquin (300 mg/kg) potentiated the anthelmintic effect of thiabendazole (750 mg/kg) on the helminth parasite, Nematospiroides dubius, in the mouse. Desmethylimipramine showed no similar potentiation.

Animals↗
PubMedDate not supplied

Determination of thiabendazole in fruit juices by a new monoclonal enzyme immunoassay.

A competitive, indirect enzyme-linked immunosorbent assay (ELISA) for thiabendazole has been developed and applied to the analysis of fruit juices spiked with this fungicide. The immunoassay is based on a new monoclonal antibody derived from a hapten functionalized at the nitrogen atom in the 1-position of the thiabendazole structure. To our knowledge, such a structure has not been previously used to obtain antibodies to thiabendazole. The I50 value and the detection limit of the ELISA for standards were 0.2 and 0.05 ng/mL, respectively. Fruit juices were analyzed by diluting samples in assay buffer, without extraction or cleanup. Samples were not even centrifuged or filtered to remove fruit pulp. Under these conditions, the immunoassay was able to accurately determine thiabendazole down to 1 ng/mL in orange and grapefruit juices, down to 5 ng/mL in banana juice, and down to 20 ng/mL in apple and pear juices. Sensitivity differences of the ELISA were caused by the minimum dilution required by each juice to minimize matrix effects: 1/10 for orange and grapefruit juices, 1/50 for banana juice, and 1/100 for apple and pear juices. In an attempt to further increase the sensitivity of the immunoassay for matrixes showing the strongest interferences, apple and pear juices spiked with thiabendazole at low levels (1-20 ng/mL) were extracted with ethyl acetate before analysis. This simple procedure entailed a significant reduction of matrix effects, which in fact allowed us to determine accurately as low as 5 ng/mL thiabendazole in apple and pear juices. Irrespective of whether samples were analyzed by the direct dilution method or after extraction, the simplicity, sensitivity, and sample throughput of this monoclonal immunoassay makes it a very convenient method for the routine monitoring of thiabendazole residues in fruit juices.

Antibodies, Monoclonal↗
PubMed2005

Artemisinin and thiabendazole are potent inhibitors of cytochrome P450 1A2 (CYP1A2) activity in humans.

OBJECTIVE: To investigate the likelihood of artemisinin and thiabendazole causing pharmacokinetic interactions involving cytochrome P450 (CYP1A2) in humans given their potent inhibitory effects on the isoform in vitro. METHODS: Ten healthy volunteers received caffeine (136.5 mg), and after a washout period of 48 h, the volunteers were given a caffeine tablet (136.5 mg) together with thiabendazole (500 mg). After an additional 14 days, the volunteers received caffeine together with artemisinin (500 mg). After each treatment, plasma was obtained up to 24 h post-dose. The plasma concentrations of the drugs were measured by HPLC with UV and MS detection. RESULTS: Using the ratio of paraxanthine to caffeine after 4 h as an indicator of CYP1A2 activity, thiabendazole and artemisinin inhibited 92 and 66%, respectively, of the enzyme activity in vivo. In addition, the pharmacokinetics of caffeine were altered in the presence of the drugs; increases in AUC(0-24) of 1.6-fold (P < 0.01) and 1.3-fold of caffeine in the presence of thiabendazole and artemisinin respectively were measured. The use of in vitro data to predict the effects of thiabendazole on the formation of paraxanthine yielded good results and underestimated the effects of artemisinin when total plasma concentrations were used. Corrections for protein binding resulted in underestimation of inhibitory effects on CYP1A2. CONCLUSIONS: Co-administration of thiabendazole or artemisinin with CYP1A2 substrates could result in clinically significant effects. Our results highlight the validity of in vitro data in predicting in vivo CYP inhibition. The formation of paraxanthine seems to be a better indicator of in vivo CYP1A2 activity than caffeine levels.

Adult↗
PubMed1984

Attempts to use thiabendazole to improve the immune response in dexamethasone-treated or stressed cattle.

Thiabendazole was evaluated in two separate experiments for its ability to enhance the immune response in dexamethasone-treated or stressed cattle. In the first experiment the cattle received either no drug treatment (controls), dexamethasone intramuscularly (IM), or dexamethasone IM plus thiabendazole orally. All animals were inoculated with heat-killed Brucella abortus strain 19, equine ferritin, tetanus toxoid, and live Corynebacterium equi at the time dexamethasone therapy was initiated. Dexamethasone (0.04 mg/kg/day IM for 3 days) significantly (p less than 0.05) inhibited the lymphocyte blastogenic response to mitogens and the antibody response to ferritin and tetanus toxoid. Thiabendazole given orally (16 mg/kg/day) beginning 24 h prior to antigen and dexamethasone administration and continued for 6 days failed to prevent the dexamethasone-induced suppression of the lymphocyte blastogenic or antibody responses. In the second experiment 51 cattle were divided into a control group and a thiabendazole-treated group. The animals were stressed by weaning, injection of antigen (equine ferritin, tetanus toxoid, B. abortus strain 19 and killed bovine viral diarrhea virus) and castration of the bulls on the day that thiabendazole therapy was started. Thiabendazole administered orally for 5 days at a dosage of 20 mg/kg did not enhance the antibody response to any of the antigens, and was associated with a significantly lower antibody response to B. abortus.

Animals↗
PubMed1993

Treatment of Strongyloides stercoralis hyperinfection syndrome with thiabendazole administered per rectum.

There is a rising interest in Strongyloides stercoralis infection due to the expanding population of immunosuppressed patients. Currently the drug of choice for both enteric and tissue forms of infection with this organism is oral thiabendazole. We report a patient with a small bowel obstruction due to S. stercoralis hyperinfection who was unable to take thiabendazole orally. Thiabendazole was administered rectally, and the hyperinfection syndrome resolved. Peak serum concentrations of thiabendazole were achieved 4 hours after rectal administration, and drug levels were sustained longer than previously reported with oral dosing. In addition, elevated levels of thiabendazole metabolites in the patient's urine further confirmed significant absorption. Rectal administration of thiabendazole should be considered for patients unable to take the medication orally.

Administration, Rectal↗
PubMed2003

Treatment of pediculosis capitis with thiabendazole: a pilot study.

BACKGROUND: Despite the improvement of health standards, head lice infestation remains a problem worldwide. In addition, there is increasing evidence that head lice are becoming resistant to common pediculocides. AIM: To test the potential effectiveness of thiabendazole, a potent and broad-spectrum antiparasitic and scabicidal agent, for the treatment of pediculosis capitis. METHODS: Twenty-three female patients, aged 7-12 years, who had active head lice infestation, were treated with oral thiabendazole, 20 mg/kg twice daily for 1 day, with repeat treatment after 10 days. RESULTS: On the 11th day, meticulous hair examination showed that 21 patients had responded to treatment [91%; 95% confidence interval (CI), 71-98%], with 14 showing complete responsiveness (61%; 95% CI, 40-78%). The only adverse reactions observed were nausea and mild dizziness, which occurred in four patients, three of whom took the drug on an empty stomach. CONCLUSIONS: Thiabendazole may be a promising treatment for head lice infestation. The primary action of this drug seems to be the inhibition of parasite microtubule polymerization by binding to beta-tubulin. In addition, thiabendazole may interfere with the synaptic transmission of lice through its probable cholinergic effect. As pediculosis capitis is a very communicable disease, the unresponsiveness to thiabendazole could largely be attributed to new infestations during the drug-free interval. Therefore, massive and simultaneous rather than individual and isolated treatments should be used to achieve the epidemiologic control of this ectoparasitosis. As this is a preliminary study, the performance of double-blind, randomized controlled trials on this subject is warranted. Thiabendazole, either alone or in combination with other agents, may prove to be of particular use in areas in which head lice show resistance to common pediculocides.

Administration, Oral↗
PubMed1990

Theophylline and antiparasitic drug interactions. A case report and study of the influence of thiabendazole and mebendazole on theophylline pharmacokinetics in adults.

To determine a change in theophylline pharmacokinetics during concomitant thiabendazole or mebendazole therapy, we studied six normal, healthy male volunteers. Aminophylline was administered intravenously, followed by a 30-h blood sampling period. Subjects were randomized to receive thiabendazole or mebendazole, then crossed over to receive the other therapy. Theophylline concentrations were measured utilizing an HPLC technique and a one-compartment model was fit to the data. Theophylline pharmacokinetic parameters were significantly different during thiabendazole therapy. Mean theophylline half-life increased, clearance decreased and elimination rate constant decreased. Two subjects experienced severe nausea and vomiting during thiabendazole therapy. There were no significant differences in theophylline pharmacokinetic parameters during mebendazole therapy. Thiabendazole administration results in a significant decrease in theophylline clearance and beta elimination rate constant. The theophylline half-life increased significantly. Concomitant administration of theophylline and thiabendazole resulted in severe nausea and vomiting. Mebendazole administration did not seem to alter theophylline pharmacokinetics.

Adult↗