Aminoglycosides in Intermittent Hemodialysis: Pharmacokinetics with Individual Dosing

Abstract

Background: Data are limited on aminoglycoside pharmacokinetic differences between acute renal failure (ARF) and chronic kidney disease (CKD) or infection survival when maintaining peak and pre-hemodialysis serum concentrations between 7 and 10 and 3.5 and 5 mg/L, respectively. Objective: To report aminoglycoside pharmacokinetic observations in a consecutive series of patients receiving intermittent hemodialysis (IHD), including treatment impact of patient-specific dosing regimens. Methods: In this prospective study, all calculated pharmacokinetic parameters used concentrations drawn more than 12 hours after the initial dose and peak concentrations at least 2 hours after the dose. Analysis included pharmacokinetic parameters in stage 5 CKD, ARF, impact of the dialysis prescription, and treatment results of individualized dosing regimens lasting more than 4 days. Results: Consecutive patients with IHD (N = 167) receiving 216 courses of aminoglycosides were evaluated. The mean ± SD volume of distribution was 0.39 ± 0.15 L/kg ideal body weight, and elimination half-life during dialysis was 4.2 ± 2.3 hours. The elimination half-life off IHD was 30% shorter in ARF (31.9 ± 20.8 h) versus 45.7 ± 24.2 hours in CKD (p < 0.001). Mean extrapolated peak concentrations and pre-IHD levels were 7.7 ± 1.6 and 3.9 ± 1.2 mg/L, respectively. A 91% treatment success rate was observed in 117 individualized treatment courses in 100 patients receiving greater than or equal to 5 days of aminoglycoside therapy. Conclusions: A large variability in aminoglycoside pharmacokinetic parameters in IHD exists, with aminoglycoside elimination off IHD significantly faster in ARF. Individualized regimens using serum concentrations drawn in patients requiring treatment (non-synergistic) targeting peak concentrations of 7–10 mg/L and pre-hemodialysis serum concentrations of 3.5–5 mg/L appears successful for eradicating infections.