Ricobendazole kinetics and availability following subcutaneous administration of a novel injectable formulation to calves.
The plasma and abomasal fluid disposition kinetics of ricobendazole (RBZ) after subcutaneous (s.c.) administration of a novel injectable formulation to calves, and the comparative plasma availability after s.c. injection of RBZ and that obtained after oral treatment with albendazole (ABZ), were characterised. Six parasite-free Holstein calves received RBZ (solution 150 mg ml(-1)) by s.c. injection at 3.75 mg kg(-1) (Experiment 1). Experiment 2 was conducted in two experimental phases; in phase I, five calves (Group A) received RBZ by s.c. injection and five animals (Group B) were orally treated with ABZ (suspension 100 mg ml(-1)), at 5 mg kg(-1). Drug treatments were reversed for each group in phase II and given at 7.5 mg kg(-1). Samples of abomasal fluid (via cannula) and jugular blood were collected over 72 hours post-treatment and analysed by HPLC. RBZ and its sulphone metabolite were detected in plasma following its s.c. administration. RBZ was rapidly absorbed, reaching the plasma Cmax at 4.5 hours post-dosing. The sulphone metabolite followed a similar kinetic pattern. Both molecules were rapidly and extensively distributed into the abomasum, being detected in abomasal fluid between 30 minutes and 36 hours post-administration. An extensive plasma/abomasum exchange process, with ionic-trapping in the abomasum, accounted for the higher AUC value (>200 per cent) obtained for RBZ in abomasum compared with plasma. The s.c. treatment with RBZ formulated as a solution resulted in a significantly greater plasma availability (measured as ABZ sulphoxide) than the oral treatment with ABZ (suspension) given at the same dose rates.
Lanusse
C E
CE
Departamento de Fisiopatología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro, Campus Universitario, Tandil, Argentina.
Virkel
G L
GL
Sanchez
S F
SF
Alvarez
L I
LI
Lifschitz
A L
AL
Imperiale
F
F
Monfrinotti
A
A
D000284:Administration, Oral; D015766:Albendazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002417:Cattle / Q000097:blood / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D007279:Injections, Subcutaneous
D000871:Anthelmintics; D015766:Albendazole; C027186:albendazole sulfoxide