RESUMEN
A 5-year-old Thoroughbred-cross mare was diagnosed with insulin-dependent diabetes mellitus. Partial glycemic control and clinical improvement were achieved with daily insulin administration for 18 mo. The mare subsequently developed evidence of hypoadrenocorticism and died. Necropsy findings included lymphocytic infiltration of the pancreas, adrenal cortex, adrenal medulla, and thyroid glands, suggestive of an immune-mediated polyendocrinopathy.
Asunto(s)
Diabetes Mellitus Tipo 1/veterinaria , Enfermedades de los Caballos/tratamiento farmacológico , Poliendocrinopatías Autoinmunes/veterinaria , Animales , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Resultado Fatal , Femenino , Enfermedades de los Caballos/diagnóstico , Caballos , Poliendocrinopatías Autoinmunes/complicaciones , Poliendocrinopatías Autoinmunes/diagnóstico , Poliendocrinopatías Autoinmunes/tratamiento farmacológicoRESUMEN
OBJECTIVE: To characterize the plasma pharmacokinetics and clinical effects of pirfenidone administered IV in healthy horses. ANIMALS: 6 adult horses. PROCEDURES: A 15 mg/kg dose of pirfenidone was administered IV over 5 minutes. Physical variables were recorded and blood samples collected prior to infusion; 2.5 minutes after beginning infusion; at the end of infusion; and at 3, 6, 9, 12, 15, 20, 25, 30, 40, 50, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 12, and 24 hours after completion of infusion. Plasma concentrations of pirfenidone and its metabolites were determined. RESULTS: Mild clinical effects, including tachycardia and muscle fasciculations, were observed during drug administration but stopped at the end of the infusion. Pirfenidone and 2 metabolites, hydroxypirfenidone and carboxypirfenidone, were detected by the end of the 5-minute infusion. Mean peak plasma concentration of pirfenidone was 182.5 micromol/L, detected at the end of the infusion. Mean peak plasma concentrations of hydroxypirfenidone and carboxypirfenidone were 1.07 and 3.4 micromol/L, respectively, at 40 minutes after infusion. No parent drug or metabolites were detected at 24 hours. Distribution of pirfenidone best fit a 2-compartment model, and the drug had mean +/- SEM elimination half-life of 86.0 +/- 4.7 minutes, mean body clearance of 6.54 +/- 0.45 mL/kg/min, and apparent volume of distribution at steady state of 0.791 +/- 0.056 L/kg. CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous administration of pirfenidone was tolerated with transient adverse affects during infusion, and drug clearance was rapid.