Selected aspects of the chemical and biological profile of triclabendazole: A widely used benzimidazole fasciolicidal agent

Abstract

Fasciolosis is a very serious parasiticdisease, caused by Fasciola hepaticaand Fasciola gigantica, which isresponsible for heavy economic losses in the production of sheep and cattle inmany countries around the world. In addition, humans and other animals,including pets, may be infected. To date, triclabendazole is the only drug tocontrol fasciolosis, being effective against immature and adult flukes alike.This book chapter focuses on selectedaspects of the chemistry and biology of triclabendazole. Detailed herein arethe different alternative syntheses of the drug, analogs and prodrugs, as wellas its physical properties, with emphasis on its solubility and itscharacteristic conformational and tautomeric structural polymorphism. Inaddition, process impurities are detailed, as well as the pharmaceuticalstability of triclabendazole against stress conditions, including acid andbasic hydrolysis, oxygen (oxidation), heat and light. Thechapter also includes not only a description of the impact of the disease, butalso the pharmacokinetics and metabolism of triclabendazole, with theproduction of different oxidation metabolites on sulfur and on the2,3-dichlorophenoxy ring. Selected analytical methods for the determination ofthe drug and its metabolites in different matrices, including from commercialtablets to biological tissues (meat, liver) and fluids (milk, plasma), arepresented and discussed. Particular emphasis is given to developments thatinclude the use of chromatographic (and hyphenated) methodologies.