Gentamicin Administration in Dialysis Patients: Before or After Hemodialysis?

Abstract

Background: Gentamicin is used to treat severe infections and has a small therapeutic window. This study aimed to optimize the dosing strategy of gentamicin in intermittently hemodialyzed patients by simulating concentration–time profiles during pre- and postdialysis dosing, based on a published pharmacokinetic model. Methods: Pharmacokinetic simulations were performed with virtual patients, including septic patients, who were treated with gentamicin and received weekly hemodialysis with an interval of 48 h–48 h–72 h. The following dosing regimens were simulated: for nonseptic patients, 5 mg/kg gentamicin was given 1 h or 2 h before dialysis or a starting dose of 2.5 mg/kg and a maintenance dose of 1.5 mg/kg immediately after dialysis were given; for septic patients, 6 mg/kg gentamicin was given 1 h or 2 h before dialysis or a starting dose of 3 mg/kg and a maintenance dose of 1.8 mg/kg immediately were given after dialysis. The mean maximum concentration (Cmax), area under the curve (AUC)24 h, and target attainment (TA) of pharmacodynamic targets were calculated and compared. The following targets were adopted from the literature: Cmax >8 mg/L and <20 mg/L and AUC24 h >70 mg·h/L and <120 mg·h/L. Results: In nonseptic patients, postdialysis dosing resulted in a TA of 35% for Cmax of >8 mg/L, 100% for <20 mg/L and AUC24 h >70 mg·h/L, and 45% for <120 mg·h/L. Dosing 2 h before dialysis resulted in a TA of 100% for Cmax of >8 mg/L, 40% for <20 mg/L, 65% for AUC24 h >70 mg·h/L, and 77% for <120 mg·h/L. Simulations of septic patients resulted in comparable outcomes with higher TAs for Cmax <20 mg/L (96%), AUC24 h >70 mg·h/L (90%), and AUC24 h <120 mg·h/L (53%) for dosing 1 h before dialysis. Conclusions: Postdialysis dosing resulted in a low TA of Cmax >8 mg/L; however, predialysis dosing ensured a high TA of Cmax >8 mg/L and acceptable TA of Cmax <20 mg/L, AUC24 h >70 mg·h/L, and AUC24 h <120 mg·h/L, which could increase the efficacy of gentamicin. Therefore, clinicians should consider predialysis dosing of gentamicin in patients undergoing intermittent hemodialysis.