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Influence of Hemodialysis on Gentamicin Pharmacokinetics, Removal During Hemodialysis, and Recommended Dosing

Kevin M. Sowinski^*,, Stephanie J. Magner^*, Aroonrut Lucksiri^*, Meri K. Scott^*,, Richard J. Hamburger^,, and Bruce A. Mueller

^* Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Purdue University, Indianapolis and West Lafayette, Indiana; Department of Medicine and Division of Nephrology, School of Medicine, Indiana University, Indianapolis, Indiana; and Department of Clinical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan

Correspondence: Dr. Kevin M. Sowinski, Purdue University, Department of Pharmacy Practice, W7555 Building, 1001 West 10th Street, Indianapolis, IN 46202-2879. Phone: 317-613-2315 (x310); Fax: 317-613-2316; E-mail: ksowinsk{at}iupui.edu

Background and Objectives: Aminoglycoside antibiotics are commonly used in chronic kidney disease stage 5 patients. The purpose of this study was to characterize gentamicin pharmacokinetics, dialytic clearance, and removal by hemodialysis and to develop appropriate dosing strategies.

Design Setting, Participants, and Measurements: Eight subjects receiving chronic, thrice-weekly hemodialysis with no measurable residual renal function received gentamicin after a hemodialysis session. Blood samples were collected serially, and serum concentrations of gentamicin were determined.

Results: Median (range) systemic clearance, volume of distribution at steady state, and terminal elimination half-life were 3.89 ml/min (2.69–4.81 ml/min), 13.5 L (8.7–17.9 L), and 39.4 h (32.0–53.6 h), respectively. Median (range) dialytic clearance, estimated amount removed, and percent maximum rebound were 103.5 ml/min (87.2–132.7 ml/min), 39.6 mg (19.7–43.9 mg), and 38.7% (0%–71.8%), respectively. Gentamicin dialytic clearance was statistically significantly related to creatinine dialytic clearance (r² = 0.52, P = 0.04), although this relationship is not likely to be strong enough to serve as a surrogate for gentamicin monitoring. The pharmacokinetic model was used to simulate gentamicin serum concentrations over a one-wk period.

Conclusions: In clinical situations where gentamicin is used as the primary therapy in a patient receiving hemodialysis with a CAHP hemodialyzer, conventional doses after each dialysis session are not as efficient at achieving treatment targets as predialysis dosing with larger doses.