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Am J Vet Res ; 60(7): 888-94, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10407485

RESUMEN

OBJECTIVE: To determine pharmacokinetics of single and multiple doses of rimantadine hydrochloride in horses and to evaluate prophylactic efficacy of rimantadine in influenza virus-infected horses. ANIMALS: 5 clinically normal horses and 8 horses seronegative to influenza A. PROCEDURE: Horses were given rimantadine (7 mg/kg of body weight, i.v., once; 15 mg/kg, p.o., once; 30 mg/kg, p.o., once; and 30 mg/kg, p.o., q 12 h for 4 days) to determine disposition kinetics. Efficacy in induced infections was determined in horses seronegative to influenza virus A2. Rimantadine was administered (30 mg/kg, p.o., q 12 h for 7 days) beginning 12 hours before challenge-exposure to the virus. RESULTS: Estimated mean peak plasma concentration of rimantadine after i.v. administration was 2.0 micrograms/ml, volume of distribution (mean +/- SD) at steady-state (Vdss) was 7.1 +/- 1.7 L/kg, plasma clearance after i.v. administration was 51 +/- 7 ml/min/kg, and beta-phase half-life was 2.0 +/- 0.4 hours. Oral administration of 15 mg of rimantadine/kg yielded peak plasma concentrations of < 50 ng/ml after 3 hours; a single oral administration of 30 mg/kg yielded mean peak plasma concentrations of 500 ng/ml with mean bioavailability (F) of 25%, beta-phase half-life of 2.2 +/- 0.3 hours, and clearance of 340 +/- 255 ml/min/kg. Multiple doses of rimantadine provided steady-state concentrations in plasma with peak and trough concentrations (mean +/- SEM) of 811 +/- 97 and 161 +/- 12 ng/ml, respectively. Rimantadine used prophylactically for induced influenza virus A2 infection was associated with significant decreases in rectal temperature and lung sounds. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of rimantadine to horses can safely ameliorate clinical signs of influenza virus infection.


Asunto(s)
Antivirales/farmacocinética , Enfermedades de los Caballos/tratamiento farmacológico , Infecciones por Orthomyxoviridae/veterinaria , Orthomyxoviridae/efectos de los fármacos , Rimantadina/farmacocinética , Administración Oral , Animales , Anticuerpos Antivirales/sangre , Antivirales/administración & dosificación , Antivirales/sangre , Antivirales/normas , Área Bajo la Curva , Disponibilidad Biológica , Embrión de Pollo , Femenino , Cromatografía de Gases y Espectrometría de Masas/veterinaria , Pruebas de Inhibición de Hemaglutinación/veterinaria , Enfermedades de los Caballos/virología , Caballos , Inyecciones Intravenosas/veterinaria , Pruebas de Sensibilidad Microbiana , Mucosa Nasal/virología , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Rimantadina/administración & dosificación , Rimantadina/sangre , Rimantadina/normas
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