First-dose pharmacokinetics of aminoglycosides in critically ill haematological malignancy patients

The primary objective of this study was to determine the volume of distribution (V_d) (L/kg) of intravenous aminoglycosides (AGs) in critically ill haematological malignancy patients. Secondary objectives were to determine the body weight (actual, ideal, adjusted or lean) that yields the most precise estimate of V_d when normalised in L/kg as well as the frequency that current first-dose strategies result in post-distributional peak concentrations (C_peak) within the target range (tobramycin 16-24 mg/L; amikacin 32-48 mg/L). In total, 58 AG doses were included (tobramycin, n = 34; amikacin, n = 24). Median V_d was 0.38 L/kg normalised per the most precise dose weight, which was actual body weight (ABW). The median dose was 445 mg (5.8 mg/kg ABW) for tobramycin and 1200 mg (13.8 mg/kg ABW) for amikacin. Target C_peak (tobramycin 20 mg/L; amikacin 40 mg/L) was achieved in only 25% of all AG episodes, with 4% exceeding the target and 71% falling below the target. Twenty-four organisms were isolated in the study sample; target C_peak achievement (tobramycin 20 mg/L; amikacin 40 mg/L) would yield a peak:minimum inhibitory concentration of 10 in 75% and 52% of organisms, respectively. In conclusion, an increased V_d of AGs was identified in this critically ill haematological malignancy patient sample, and current dosing yielded a suboptimal C_peak in the majority of patients.