Population pharmacokinetic modelling of gentamicin and vancomycin in patients with unstable renal function following cardiothoracic surgery

Staatz, C. and Byrne, C. and Thomson, A.H. (2006) Population pharmacokinetic modelling of gentamicin and vancomycin in patients with unstable renal function following cardiothoracic surgery. British Journal of Clinical Pharmacology, 61 (2). pp. 164-176. ISSN 0306-5251 (http://dx.doi.org/10.1111/j.1365-2125.2005.02547.x)

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Abstract

To describe the population pharmacokinetics of gentamicin and vancomycin in cardiothoracic surgery patients with unstable renal function. Data collected during routine care were analyzed using NONMEM. Linear relationships between creatinine clearance (CL Cr) and drug clearance (CL) were identified,and two approaches to modelling changing CL Crwere examined. The first included baseline (BCOV) and difference from baseline (DCOV) effects and the second allowed the influence of CL Cr to vary between individuals. Final model predictive performance was evaluated using independent data. The data sets were then combined and parameters re-estimated. Data collected during routine care were analyzed using NONMEM. Linear relationships between creatinine clearance (CL Cr) and drug clearance (CL) were identified, and two approaches to modelling changing CL Cr were examined. The first included baseline (BCOV) and difference from baseline (DCOV) effects and the second allowed the influence of CL Cr to vary between individuals. Final model predictive performance was evaluated using independent data. The data sets were then combined and parameters re-estimated. A parameter describing individual changes in CL cr with time improves population pharmacokinetic modelling of gentamicin but not vancomycin in clinically unstable patients.

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