Pharmacokinetic Analysis of Once-Daily Gentamicin in Immune-Compromised Adults with Normal Renal Function

Abstract

Objective To analyze and compare the pharmacokinetic parameters of a single daily dose (SDD) of gentamicin 5 mg/kg in adults with normal renal function who developed neutropenic fever during intensive non-nephrotoxic chemotherapy. Methods Ten patients received gentamicin in a 60-minute infusion and blood samples were drawn at 0, 0.5, 1, 2, 8, and 24 hours after the end of the infusion. Gentamicin concentrations were fitted to a noncompartment analysis (NCA) model and a 2-compartment open model for comparison. Results The mean ± SD gentamicin concentrations were: maximum concentration at 0.5 hours, 15.7 ± 3.4 mg/L; at 1 hour, 12.3 ± 2.3 mg/L; at 2 hours, 8.3 ± 2.5 mg/L; and at 8 hours, 1.7 ± 1 mg/L. The minimum concentration at 24 hours was 0.27 ± 0.36 mg/L. No statistical differences were established between the mean AUC (63 ± 8.5 and 54.2 ± 9.9 mg/L · h; p = 0.5) and gentamicin clearance (101.0 ± 13.3 and 160.6 ± 27.3 mL/min; p = 0.065). Statistical differences were demonstrated between the mean elimination rate constant (p < 0.001), half-life (p < 0.001), and volume of distribution (p < 0.001), measured by the NCA and the 2-compartment models. Conclusions Based on our findings, the NCA method for kinetic analysis of gentamicin prescribed in high SDD can be applied only for AUC and gentamicin clearance calculations.