Effect of dietary nitrogen intake on gentamicin disposition in sheep

The effect on gentamicin pharmacokinetics of a diet high (HP) (120 g/day) or low (LP) (25 g/day) in digestible proteins was studied in sheep. Gentamicin sulphate (4 mg/kg) and inulin (40 mg/kg) were administered by the intravenous route to six ewes of local Moroccan breed. The serum gentamicin concentrations were consistently higher in ewes that received a LP diet. Clearance was 0.93 +/- 0.13 ml/mm/kg in the LP group and 1.64 +/- 0.40 ml/mm/kg in the HP group. The volume of distribution at steady state (Vss) was lower in the LP group (11% of body weight) than in the HP group (21.8% of body weight). These diet-linked variations in pharmacokinetic parameters were also obtained in the disposition of inulin following the intravenous administration of a single dose. This suggests that the protein content of the diet modifies the distribution of body water and kidney function. The therapeutic, toxicological and hygienic implications of these modifications are discussed.