RESUMEN
A urinary metabolite of flunixin in greyhound dogs was isolated and purified by a gradient-elution solid-phase extraction technique. The purified metabolite was shown to be hydrolyzed to free flunixin by strong base and by beta-glucuronidase, suggesting the presence of a C1-beta-glucuronide ester of flunixin. The metabolite was further characterized by positive-ion, tandem MS with electrospray ionization. Mass spectral data showed the presence of a protonated molecular ion (M+1) at m/z 473, which was consistent with the molecular weight of protonated flunixin glucuronide, and a product ion at m/z 297, which was consistent with the molecular weight of protonated flunixin. Collisionally induced dissociation of the m/z 297 product ion showed a fragmentation pattern consistent with that of standard flunixin. These data support the contention that this metabolite of flunixin in greyhound urine is the C1-beta-glucuronide of flunixin. Acyl glucuronide metabolites of some organic acid drugs have been shown to bind covalently to tissue proteins in vitro, in vivo, and ex vivo. The presence of this metabolite may, therefore, have pharmacokinetic and pharmacodynamic implications for flunixin in greyhound dogs, as well as in other animal species in which the acyl glucuronide of flunixin is a metabolite.
Asunto(s)
Analgésicos/orina , Antiinflamatorios no Esteroideos/orina , Clonixina/análogos & derivados , Animales , Cromatografía Líquida de Alta Presión , Clonixina/aislamiento & purificación , Clonixina/orina , Perros , Espectrometría de MasasRESUMEN
Gastric hypersecretion following administration of tolazoline resulted in severe hypochloremic alkalosis in an infant with persistent fetal circulation. An initial bolus injection of 2 mg/kg was followed by an infusion of 5 mg/kg/hr for 24 hours. The infusion was then maintained at 2 mg/kg/hr for the next four days. Volume of gastric secretions exceeded 25 ml/kg/24 hr. Weaning from tolazoline and replacement of chloride and potassium corrected the metabolic alkalosis.