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Dosing of Gentamicin in Patients With End‐Stage Renal Disease Receiving Hemodialysis
Author(s) -
Teigen Mette Maja B.,
Duffull Stephen,
Dang Lily,
Johnson David W.
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006292987
Subject(s) - dosing , hemodialysis , medicine , gentamicin , nonmem , dialysis , population , end stage renal disease , pharmacokinetics , urology , renal function , elimination rate constant , creatinine , volume of distribution , antibiotics , chemistry , biochemistry , environmental health
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.