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.
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.
Mestorino
N
N
Cátedra de Farmacología, Farmacotécnia y Terapéutica, Facultad de Ciencias Veterinarias, Universidad Nacional de la Plata, La Plata, Argentina.
Formentini
E A
EA
Lucas
M F
MF
Fernandez
C
C
Modamio
P
P
Hernández
E Mariño
EM
Errecalde
J O
JO
D000818:Animals; D000871:Anthelmintics / Q000097:blood / Q000493:pharmacokinetics*; D001562:Benzimidazoles / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002417:Cattle / Q000378:metabolism*; D005260:Female; D007408:Intestinal Absorption / Q000502:physiology*; D012756:Sheep / Q000378:metabolism*; D013454:Sulfoxides / Q000097:blood / Q000378:metabolism*; D000077682:Triclabendazole
D000871:Anthelmintics; D001562:Benzimidazoles; D013454:Sulfoxides; D000077682:Triclabendazole; C085104:triclabendazole sulfoxide