Pharmacokinetics and renal toxicity of three once-a-day doses of amikacin in cows

Abstract

Pharmacokinetic variables of amikacin in cows were determined after administration of amikacin sulphate either intravenously (IV) or intramuscularly (IM) at a dose of 25 mg/kg per day for three days. Amikacin concentrations at time zero and maximum serum concentrations were 240.8 µg/mL and 122.53 µg/mL, respectively. The elimination half-life remained unchanged during the three days of administration (T½ß = 1.33 ± 0.029 h for the IV route and T½ß = 2.75 ± 0.38 h for the IM route). Apparent volumes of distribution suggest limited distribution out of the central compartment (VdAUC = 0.154 ± 0.005 L/kg; Vdc = 36.50 ± 2.35 L; Vdss = 0.092 ± 0.004 L/kg). Bioavailability after IM administration was 95%. Serum profiles of urea, creatinine, albumin, electrolytes and pH after 5-day treatment with amikacin at a dose of 25 mg/kg per day IM revealed no changes. Assessment of diffusion of amikacin to milk by a commercially available screening method to detect antibiotic residues revealed that amikacin could not be detected by the fifth milking period after the last treatment. These results suggest that it would be rational to use a large single-daily dose of amikacin for future clinical trials in cows.