Gentamicin Administration in Dialysis Patients: Before or After Hemodialysis?

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.

Shedding a Light on Acyclovir Pharmacodynamics: A Retrospective Analysis on Pharmacokinetic/Pharmacodynamic Modelling of Acyclovir for the Treatment of Varicella Zoster Virus Infection in Immunocompromised Patients: A Pilot Study.

BACKGROUND: Acyclovir and valacyclovir are used for the treatment and prophylaxis of infections with herpes simplex virus (HSV) and varicella zoster virus (VZV). The aim of this study is to provide insight into the pharmacodynamics (PD) of (val)acyclovir. METHODS: Patients were retrospectively selected, based on therapeutic drug monitoring for acyclovir, to create a population pharmacokinetic (PK) model in Pmetrics. This PK model was used to develop a PK/PD model to study the effect of acyclovir levels on VZV viral load in plasma in immunocompromised patients. RESULTS: Immunocompromised patients with known VZV viral loads in plasma were included for PK/PD modelling (N = 4, with 23 measure points); they were part of the population of 43 patients used for PK model building. The PK/PD model described the data well (r2 = 0.83). This is a hopeful first step in clarifying the pharmacodynamics of acyclovir; however, the data in this study are limited. CONCLUSIONS: Our preliminary PK/PD model can be used in further research to determine the effect of acyclovir levels on VZV viral load.