title: Pharmacokinetics, efficacy prediction indexes, and residue depletion of ribavirin in Atlantic salmon's (Salmo salar) muscle after oral administration in feed.
abstract: Ribavirin is an antiviral used in human medicine, but it has not been authorized for use in veterinary medicine although it is effective against infectious salmon anemia (ISA) virus, between others. In this study, we present a pharmacokinetic profile of ribavirin in Atlantic salmon (Salmo salar), efficacy prediction indexes, and the measure of its withdrawal time. To determine the pharmacokinetic profile, fishes were orally administered with a single ribavirin dose of 1.6 mg/kg bw, and then, plasma concentrations were measured at different times. From the time-vs.-concentration curve, Cmax = 413.57 ng/mL, Tmax  = 6.96 h, AUC = 21394.01 μg·h/mL, t1/2  = 81.61 h, and K10  = 0.0421/h were obtained. Ribavirin reached adequate concentrations during the pharmacokinetic study, with prediction indexes of Cmax /IC50  = 20.7, AUC/IC50  = 1069.7, and T>IC50  = 71 h, where IC is the inhibitory concentration 50%. For ribavirin depletion study, fishes were orally administered with a dairy dose of 1.6 mg/kg bw during 10 days. Concentrations were measured on edible tissue on different days post-treatment. A linear regression of the time vs. concentration was conducted, obtaining a withdrawal time of 1966 °C days. Results obtained reveal that the dose of 1.6 mg/kg bw orally administered is effective for ISA virus, originating a reasonable withdrawal period within the productive schedules of Atlantic salmon.
authors.affiliation: Department of Clinical Sciences, Veterinary Pharmacology Laboratory, Faculty of Livestock and Veterinary Sciences, University of Chile, Santiago, Chile.
authors.forename: B
authors.initials: B
authors.lastname: San Martín
authors.affiliation: Department of Clinical Sciences, Veterinary Pharmacology Laboratory, Faculty of Livestock and Veterinary Sciences, University of Chile, Santiago, Chile.
authors.forename: R
authors.initials: R
authors.lastname: Muñoz
authors.affiliation: Department of Preventive Medicine, Food Sciences Unit, Faculty of Livestock and Veterinary Sciences, University of Chile, Santiago, Chile.
authors.forename: J
authors.initials: J
authors.lastname: Cornejo
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Martínez
authors.affiliation: Department of Clinical Sciences, Veterinary Pharmacology Laboratory, Faculty of Livestock and Veterinary Sciences, University of Chile, Santiago, Chile.
authors.forename: C
authors.initials: C
authors.lastname: Araya-Jordán
authors.affiliation: Department of Clinical Sciences, Veterinary Pharmacology Laboratory, Faculty of Livestock and Veterinary Sciences, University of Chile, Santiago, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Maddaleno
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Anadón
mesh_terms: D000284:Administration, Oral; D000821:Animal Feed; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D017756:Aquaculture; D004350:Drug Residues / Q000032:analysis / Q000493:pharmacokinetics; D018482:Muscle, Skeletal / Q000737:chemistry*; D012254:Ribavirin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D020317:Salmo salar / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin