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.

Efficacy Prediction of Four Pharmaceutical Formulations for Intramammary Administration Containing Aloe vera (L.) Burm. f. Combined With Ceftiofur or Cloxacillin in Lactating Cows as an Alternative Therapy to Treat Mastitis Caused by Staphylococcus aureus

“…In particular, the three most commonly used indices are: the ratio between the maximum concentration reached of an antimicrobial and the MIC value (C max /MIC), the fraction of dosing interval in which the antimicrobial concentration remains above the MIC (T > MIC), and the ratio between the area under the concentration-time curve and the MIC value (AUC/MIC). The process of calculating these efficacy indices has become the gold standard for both the assessment of PK/PD and as a guide for the establishment of dosing regimens (32)(33)(34).…”