Pharmacologic factors associated with gentamicin nephrotoxicity in rabbits

Nine rabbits were given subcutaneous doses of 7.5 mg of gentamicin/kg every 24 hr, and nine were given 2.5 mg of gentamicin/kg every 8 hr for three weeks or longer. Renal function was evaluated by monitoring of the concentration of creatinine in serum and the rate of clearance of gentamicin from serum. In the animals receiving the 8-hr divided dosage, a deterioration of renal function as early as day 7 was demonstrated by the rate of clearance of gentamicin, and deterioration by day 21 was evidenced by the concentration of creatinine in serum; the renal function of the animals receiving the single daily dose was unchanged. There was no relationship between peak or trough concentrations of gentamicin in serum and the development of nephrotoxicity. The animals receiving the 8-hr dosages had a significantly longer daily duration of exposure to concentrations of ~O.l, ===1.0, ===2.0, and ~3.0 t-tg of gen-tamicin/ml in serum than did animals receiving the daily dosage. Gentamicin is an aminoglycoside antibiotic ac-tive against many organisms, but it has a narrow therapeutic index because of renal and eight