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Development of a Semimechanistic Model to Describe the Pharmacokinetics of Gentamicin in Patients Receiving Hemodialysis

From the School of Pharmacy, University of Queensland, Brisbane, Australia.

The aim of this study was to ascertain the most suitable dosing schedule for gentamicin in patients receiving hemodialysis. We developed a model to describe the concentration-time course of gentamicin in patients receiving hemodialysis. Using the model, an optimal dosing schedule was evaluated. Various dosing regimens were compared in their ability to achieve maximum concentration (C_max, 8 mg/L) and area under the concentration time-curve (AUC 70 mg·h/L and 120 mg·h/L per 24 hours). The model was evaluated by comparing model predictions against real data collected retrospectively. Simulations from the model confirmed the benefits of predialysis dosing. The mean optimal dose was 230 mg administered immediately before dialysis. The model was found to have good predictive performance when simulated data were compared to data observed in real patients. In summary, a model was developed that describes gentamicin pharmacokinetics in patients receiving hemodialysis. Predialysis dosing provided a superior pharmacokinetic profile than did postdialysis dosing.

Key Words: Gentamicin • pharmacokinetics • hemodialysis

Address for reprints: Stephen Duffull, PhD, School of Pharmacy, University of Queensland, St Lucia, 4072, Brisbane, Australia; e-mail: sduffull{at}pharmacy.uq.edu.au.

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