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

Abstract

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 (r 2 ‫؍‬ 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.

Pharmacokinetics of Sulfobutylether-Beta-Cyclodextrin and Voriconazole in Patients with End-Stage Renal Failure during Treatment with Two Hemodialysis Systems and Hemodiafiltration

“…Intradialytic administration of drugs is rarely used, since unintended drug removal is to be avoided. Predialytic drug administration is sometimes used to maintain intradialytic concentrations of antiepileptics in patients with seizures and has been tried for administration of aminoglycosides and carboplatin (7,14,16). The present study provides evidence that intradialytic administration could be a better choice for voriconazole-SBECD in order to remove the solvent from the circulation.…”

Gentamicin Dosing and Monitoring Challenges in End-Stage Renal Disease

“…A novel method, pre-dialysis gentamicin dosing [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] has been described as being similar to once-daily dosing in patients with normal renal function [12]. This dosing strategy allows for higher gentamicin doses and serum concentrations.…”

Management of Aminoglycosides in the Intensive Care Unit

“…The readers are referred to other more comprehensive reviews for dosing and monitoring recommendations. [70][71][72] Therapeutic Drug Monitoring Therapeutic drug monitoring (TDM) of aminoglycosides is essential not only to assess efficacy but also in the prevention of toxicity because of their narrow therapeutic index. Aminoglycosides are well known to be nephrotoxic; however, as mentioned previously, by using patient-specific TDM, the incidence of nephrotoxicity may be reduced.…”