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Effects of dose and duration of therapy on gentamicin tissue residues in sheep

Effects of dose and duration of therapy on gentamicin tissue residues in sheep

American Journal of Veterinary Research 47(11): 2373-2379

The effects of different doses and dosage regimens on gentamicin pharmacokinetics and tissue residues were determined. Five groups of 12 sheep each were given gentamicin IM: group I, 2 mg of gentamicin sulfate/kg once; group II, 6 mg/kg once; group III, 18 mg/kg once; group IV, 6 mg/kg every 24 hours for 3 doses; and group V, 2 mg/kg every 8 hours for 9 doses. Serum concentrations were determined serially until sheep were killed and necropsied. Three sheep from each group were killed at 1, 4, 8, and 12 days after the last dose was administered. Renal cortex, renal medulla, liver, spleen, lung, skeletal muscle, and skeletal muscle at the injection site were assayed for gentamicin. An exponential equation was fitted to the serum concentrations, and various pharmacokinetic variables were determined. Serum clearance tended to increase as the single dose increased (P = 0.0588). Steady-state volume of distribution increased as the single dose was increased (P < 0.05). Renal cortex contained the highest concentration of gentamicin which decreased in a biexponential manner. Concentrations in all tissues, except the injection site, were dependent upon the amount of the total dose, not the size of the injected dose (P < 0.05). Concentrations at the injection site were up to 29 .mu.g/g of tissue at 1 day after the last dose was given and were dependent upon the amount of total dose from multiple injections, not on the amount of each injected dose (P < 0.05). These results indicated that tissue residues increased as the total dose gentamicin was increased or as the duration of gentamicin therapy was increased. Furthermore, the injection site contained substantial amounts of gentamicin at 1 day after the last dose was given.

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Accession: 001580550

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PMID: 3789497

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