RESUMO
BACKGROUND: Aminoglycoside antibiotic efficacy is related to peak concentration (C(max)) and postantibiotic effect, whereas toxicity is directly related to body exposure as measured by area under the serum concentration versus time curve (AUC). On the basis of pharmacokinetic simulation models, tobramycin administration during the first 30 min of high-flux hemodialysis achieves similar C(max) but significantly lower AUC and prehemodialysis concentrations compared with conventional dosing in the last 30 min of hemodialysis. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: To test this hypothesis, a pilot study in which five adult chronic hemodialysis patients who were undergoing high-flux dialysis received one dose of tobramycin 1.5 mg/kg intravenously during the first or last 30 min of hemodialysis was conducted. After a 1-mo washout period, patients crossed over to the other treatment schedule. Tobramycin serum concentrations were measured to determine C(max), interdialytic and intradialytic elimination rate constants and half-lives, AUC, and clearance. RESULTS: Tobramycin administration during the first and last 30 min of hemodialysis resulted in similar C(max) of 5.63 +/- 0.49 and 5.83 +/- 0.67 mg/L (P > 0.05) but significantly lower prehemodialysis concentrations of 0.16 +/- 0.09 and 2.44 +/- 0.43 mg/L (P < 0.001) and AUC of 21.06 and 179.23 +/- 25.84 mg/h per L (P < 0.001), respectively. CONCLUSIONS: Tobramycin administration during the first 30 min of hemodialysis results in similar C(max) but lower AUC to conventional dosing, which may translate into comparable efficacy but lower toxicity.