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 (C max ), 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: C max >8 mg/L and <20 mg/L and AUC 24 h >70 mg·h/L and <120 mg·h/L. RESULTS: In nonseptic patients, postdialysis dosing resulted in a TA of 35% for C max of >8 mg/L, 100% for <20 mg/L and AUC 24 h >70 mg·h/L, and 45% for <120 mg·h/L. Dosing 2 h before dialysis resulted in a TA of 100% for C max of >8 mg/L, 40% for <20 mg/L, 65% for AUC 24 h >70 mg·h/L, and 77% for <120 mg·h/L. Simulations of septic patients resulted in comparable outcomes with higher TAs for C max <20 mg/L (96%), AUC 24 h >70 mg·h/L (90%), and AUC 24 h <120 mg·h/L (53%) for dosing 1 h before dialysis. CONCLUSIONS: Postdialysis dosing resulted in a low TA of C max >8 mg/L; however, predialysis dosing ensured a high TA of C max >8 mg/L and acceptable TA of C max <20 mg/L, AUC 24 h >70 mg·h/L, and AUC 24 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.
