Indications
Triclabendazole is specifically indicated for the treatment of fascioliasis in patients aged six years and older. This antiparasitic medication effectively targets the liver fluke infections caused by Fasciola hepatica and Fasciola gigantica.
Pharmacodynamics
Triclabendazole, along·h its metabolites, exhibits efficacy against both immature and mature stages of Fasciola hepatica and Fasciola gigantica helminths. It should be noted that this drug has the potential to prolong·he cardiac QT interval. Therefore, it is essential to monitor the ECG of patients with a history of QT prolong·hose who are concurrently using·her medications known to influence the QT interval.
Absorption
Following·he oral administration of a sing·h a 560-calorie meal to patients diagnosed with fascioliasis, mean peak plasma concentrations (Cmax) were observed at 1.16 μmol/L for triclabendazole, 38.6 μmol/L for the sulfoxide metabolite, and 2.29 μmol/L for the sulfone metabolite. The area under the curve (AUC) for these substances was recorded as 5.72 μmol·h/L, 386 μmol·h/L, and 30.5 μmol·h/L, respectively. The time to reach maximum concentration (Tmax) for both the parent compound and the active sulfoxide metabolite was between 3 to 4 hours. Notably, co-administration with a meal significantly enhances absorption, increasing·he sulfoxide metabolite by approximately 2 to 3 times, with the sulfoxide metabolite Tmax extending·hours in fasting·hours when fed.
Metabolism
Triclabendazole undergoes significant metabolic transformation predominantly via the CYP1A2 enzyme, responsible for converting·hermore, it is metabolized to a lesser extent by CYP2C9, CYP2C19, CYP2D6, CYP3A, and flavin-containing·he sulfoxide metabolite is further processed mainly by CYP2C9 into the active sulfone metabolite, with minor contributions from CYP1A1, CYP1A2, CYP1B1, CYP2C19, CYP2D6, and CYP3A4.
Mechanism of Action
Triclabendazole functions as an anthelmintic agent targeting Fasciola species, although the exact mechanism of action remains not fully elucidated. Research conducted in vitro and in animal models indicates that triclabendazole and its active metabolites, sulfoxide and sulfone, are absorbed by the tegument of both immature and mature flukes. This absorption leads to a decrease in resting membrane potential, inhibition of tubulin function, and disruption of crucial protein and enzyme synthesis necessary for the parasite's survival. As a result, these metabolic disturbances impair the motility of the flukes, disrupt their outer surface, and inhibit processes such as spermatogenesis and the development of egg and embryonic cells. However, studies suggest that there is a potential for resistance to develop against triclabendazole. This resistance could arise from multifactorial mechanisms, including alterations in drug uptake or efflux processes, modification of target molecules, or changes in drug metabolism. The clinical significance of resistance to triclabendazole in human populations has yet to be determined.
