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

Comparative Metabolism of Thiabendazole in Cultured Hepatocytes from Rats, Rabbits, Calves, Pigs, and Sheep, Including the Formation of Protein-Bound Residues

“…4-Hydroxythiabendazole, formed by hydroxylation of the benzimidazole ring at the 4-position, was reported as a minor metabolite of TBZ in cow urine (Gardiner et al, 1974). In rodents, both Nmethylthiabendazole and 2-acetylbenzimidazole have been identified as minor urinary metabolites (Tsuchiya et al, 1987;Fujitani et al, 1991). Furthermore, TBZ has been said to bind irreversibly to tissue proteins in mouse embryos through a putative cytochrome P450mediated mechanism (Yoneyama et al, 1985;Yoneyama and Ichikawa, 1986).…”

In Vitro and in Silico Identification and Characterization of Thiabendazole as a Mechanism-Based Inhibitor of CYP1A2 and Simulation of Possible Pharmacokinetic Drug-Drug Interactions

“…1. Proposed biotransformation of TBZ (its elimination and bioactivation) (Fujitani et al, 1991;Mizutani et al, 1994;Coulet et al, 2000;Dalvie et al, 2006). assays on the effect of TBZ and 5OH-TBZ on CYP1A2 and TBZ on CYP2C9 and 3A4 activities (Table 1).…”

“…The major route is the CYP1A2-catalyzed hydroxylation to 5-hydroxythiabendazole, which is further metabolized to glucuronide and sulfate conjugates (Coulet et al, 1998). Other metabolites identified include 4-hydroxythiabendazole, 2-acetylbenzimidazole, N-methylthiabendazole, and benzimidazole (Fujitani et al, 1991). TBZ has also been shown to induce members of the CYP1A and CYP2B family in rats in vivo (Price et al, 2004) and rabbit CYP1A2 in vitro (Aix et al, 1994), which implies the possibility of the compound inducing its own metabolism.…”

In vitro and in vivo metabolite identification of a novel benzimidazole compound ZLN005 by liquid chromatography/tandem mass spectrometry

“…Several major metabolites of thiabendazole were identified in vitro and in vivo in a previous report. 18 Major metabolites of thiabendazole arise from hydroxylation of the 4-and 5-benzimidazole sites, and further conjugation of glucuronide and sulfate groups. The metabolites we identified for ZLN005 are consistent with those identified for thiabendazole in these previous studies except that only the 5-OH metabolite was detected.…”