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.
Departamento de Fisiopatología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro, Campus Universitario, Tandil, Argentina.
C E
CE
Lanusse
G L
GL
Virkel
S F
SF
Sanchez
L I
LI
Alvarez
A L
AL
Lifschitz
F
F
Imperiale
A
A
Monfrinotti
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