Pharmacokinetic disposition of triclabendazole in cattle and sheep; discrimination of the order and the rate of the absorption process of its active metabolite triclabendazole sulfoxide

Abstract

A comparative pharmacokinetic study was conducted to determine the order and the rate of absorption of triclabendazole (TCBZ) in cattle and sheep. A commercial suspension of TCBZ (Biofasiolex, Biogénesis S.A., Argentina) was administered at a dose rate of 10 mg/kg by the oral route to six Holstein female calves and six Corriedale female sheep. The plasma concentration profiles of the metabolites triclabendazole sulfoxide (TCBZ-SO) and triclabendazole sulfone (TCBZ-SO(2)) were analysed by means of the non-compartmental method. The order of the absorption process of the active metabolite, TCBZ-SO, was determined by construction of curves of cumulative absorbed fraction of the drug by means of the Wagner-Nelson method. The appearance of TCBZ-SO in plasma of cattle and sheep resembles the entry of a constant quantity of drug into the organism per unit time. This is explained by the reservoir effect of the rumen, which acts as a biological slow-release system for TCBZ-SO and its precursor TCBZ to the posterior digestive tract where they are absorbed. The plasma concentration profiles of TCBZ-SO in both species were well described by a one-compartment open model with zero-order process of absorption and first-order process of elimination. The values of AUC(0-infinity) and C(max) of TCBZ-SO did not differ between species, while other kinetic parameters except for lambda(z) had higher values in calves than in sheep. In the case of TCBZ-SO(2), t(max) was the only parameter that did not differ between species, while other kinetic parameters except for lambda(z) had higher values in calves than in sheep.

Reducing the future threat from (liver) fluke: realistic prospect or quixotic fantasy?

“…A similar time-scale of TCBZ action against juvenile (4-week-old) flukes was described by Halferty et al (2008). The pattern of removal of adult flukes fits in well with the known pharmacokinetics of the drug in sheep, as it follows the peak plasma concentrations of the two main metabolites, TCBZ.SO and TCBZ.SO 2 , which are reached at 22 h and 36 h pt, respectively, following oral dosing (Mestorino et al, 2008). A severe necrosis of the posterior half of the body was observed at 72 h pt and, by 96 h pt, the tegument had been completely stripped off (Toner et al, 2010a).…”

Fasciola hepatica: time-dependent disruption of spermatogenesis following in vivo treatment with triclabendazole

“…A sharp drop in fluke numbers occurred between 72 and 96 h pt (Toner et al 2010a). The reduction in motility and elimination follow on from the peaks in plasma concentration of the sulphoxide and sulphone metabolites: at 18-22.5 h and 36-39 h pt, respectively, depending on the route of administration of TCBZ (either oral or intra-ruminal: Hennessy et al 1987;Mestorino et al 2008;Ceballos et al Fig. 9-12 Micrograph (9) and transmission electron micrographs (10-12) of the testis tubules of 12-week-old F. hepatica recovered from the gall bladder 96 h following treatment with triclabendazole (10 mg/kg).…”

Determination of Triclabendazole in Cattle Plasma as Its Sulphoxide and Sulphone Metabolites by Rotating Disk Sorptive Extraction Combined With High-Performance Liquid Chromatography and Its Application to Pharmacokinetic Studies

“…This method results in a greener and simpler alternative compared with methods based on SPE. [5][6][7][8] In addition, the extraction device is reusable and easily built in the laboratory.…”

“…1,4 A number of analytical methods have been described to determine TCB and its metabolites in different matrices. [5][6][7][8][9][10][11][12] The simultaneous determination of TCB and its metabolites has been reported in bovine and goat tissues by using an extraction of analytes from the tissues with acetonitrile, and then crude extracts are subjected to liquid-liquid extraction with n-hexane. 9,10 A traditional liquid-liquid extraction has also been described for separation/ determination of TCB from spiked human plasma using ethyl acetate.…”