title: Comparative disposition of ricobendazole enantiomers after intravenous and subcutaneous administration of a racemic formulation to calves.
abstract: The enantioselective disposition kinetics of the benzimidazole anthelmintic, ricobendazole (RBZ), have been characterized after its intravenous (iv) and subcutaneous (sc) administration as a racemic formulation to cattle. The (+) and (-) RBZ enantiomeric forms were recovered in plasma after iv and sc administration of the racemic RBZ formulation, using a chiral phase based HPLC method. A biexponential plasma concentration versus time curve was observed for both RBZ enantiomers following the iv treatment. Total body clearance was higher for (-) RBZ (150.4 mL/h. kg) compared with that obtained for the (+) RBZ antipode (78.1 mL/h. kg). The elimination half-life of the (-) RBZ enantiomer was shorter (T1/2beta: 2.67 h) compared with the (+) enantiomer (T1/2beta: 5.41 h). The plasma availability (expressed as AUC) was significantly higher for (+) RBZ compared with that obtained for the (-) antipode following both treatments. The enantiomeric ratio in plasma at T(0) was close to unity (50% of each enantiomer); the analysis of the concentration ratios (+) RBZ/(-) RBZ, demonstrated an increase in the proportion of (+) RBZ during the time course of the kinetics after both iv and sc treatments. The results presented herein show the enantioselective disposition kinetics of RBZ in cattle and are a further contribution to the understanding of the kinetic behaviour of these sulphoxide-containing benzimidazole anthelmintics in ruminants.
authors.affiliation: Departament de Farmacologia i Terapèutica, Facultat de Veterinària, UAB, 08193 Bellaterra, Spain. ccristofol@quiro.uab.es
authors.forename: C
authors.initials: C
authors.lastname: Cristòfol
authors.forename: G
authors.initials: G
authors.lastname: Virkel
authors.forename: L
authors.initials: L
authors.lastname: Alvarez
authors.forename: M
authors.initials: M
authors.lastname: Arboix
authors.forename: C E
authors.initials: CE
authors.lastname: Lanusse
mesh_terms: D015766:Albendazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D000465:Algorithms; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001711:Biotransformation; D002417:Cattle; D006207:Half-Life; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D013237:Stereoisomerism; D013450:Sulfones / Q000378:metabolism
chemical_list: D000871:Anthelmintics; D013450:Sulfones; D015766:Albendazole; C027186:albendazole sulfoxide