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Dosing of Gentamicin in Patients With End-Stage Renal Disease Receiving Hemodialysis

From the School of Pharmacy, University of Queensland, Brisbane, Australia (Ms Teigen, Dr Duffull, Ms Dang); Diakonhjemmet Hospital Pharmacy, Oslo, Norway (Ms Teigen); the Department of Renal Medicine, University of Queensland at Princess Alexandra Hospital, Brisbane, Australia (Dr Johnson); and the School of Pharmacy, University of Otago, Dunedin, New Zealand (Dr Duffull).

The aim of this study was to evaluate dosing schedules of gentamicin in patients with end-stage renal disease and receiving hemodialysis. Forty-six patients were recruited who received gentamicin while on hemodialysis. Each patient provided approximately 4 blood samples at various times before and after dialysis for analysis of plasma gentamicin concentrations. A population pharmacokinetic model was constructed using NONMEM (version 5). The clearance of gentamicin during dialysis was 4.69 L/h and between dialysis was 0.453L/h. The clearance between dialysis was best described by residual creatinine clearance (as calculated using the Cockcroft and Gault equation), which probably reflects both lean mass and residual clearance mechanisms. Simulation from the final population model showed that predialysis dosing has a higher probability of achieving target maximum concentration (C_max) concentrations (>8 mg/L) within acceptable exposure limits (area under the concentration-time curve [AUC] values >70 and <120 mg·h/L per 24 hours) than postdialysis dosing.

Key Words: Aminoglycosides • hemodialysis • end-stage renal disease • pharmacokinetics

Address for reprints: Stephen Duffull, MPharm, PhD, School of Pharmacy, University of Otago, Dunedin, New Zealand; e-mail: stephen.duffull{at}stonebow.otago.ac.nz.

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