Figure 117

Course of serum concentrations, A, and of renal cortical concentrations, B, of gentamicin, netilmicin, tobramycin, and amikacin after dosing by a 30-minute intravenous injection or continuous infusion over 24 hours [10,11].

Two trials in humans found that the dosage schedule had a critical effect on renal uptake of gentamicin, netilmicin [10], amikacin, and tobramycin [11]. Subjects were patients with normal renal function (serum creatinine concentration between 0.9 and 1.2 mg/dL, proteinuria lower than 300 mg/24 h) who had renal cancer and submitted to nephrectomy. Before surgery, patients received gentamicin (4.5 mg/kg/d), netilmicin (5 mg/kg/d), amikacin (15 mg/kg/d), or tobramycin (4.5 mg/kg/d) as a single injection or as a continuous intravenous infusion over 24 hours. The single-injection schedule resulted in 30% to 50% lower cortical drug concentrations of netilmicin, gentamicin, and amikacin as compared with continuous infusion. For tobramycin, no difference in renal accumulation could be found, indicating the linear cortical uptake of this particular aminoglycoside [8]. These data, which supported decreased nephrotoxic potential of single-dose regimens, coincided with new insights in the antibacterial action of aminoglycosides (concentration-dependent killing of gram-negative bacteria and prolonged postantibiotic effect) [12]. N.S.—not significant.

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