Ahmed N. Mohamed

Amin NB

Brian S. Decker

Craig WA

Dager WE

Dang L

Decker BS

Drusano GL

Green B

Kevin M. Sowinski

Le T

Leypoldt JK

Mary Chambers

Michael A. Kraus

Sharon M. Moe

Sowinski KM

Teigen MM

Vercaigne LM

Vos PF

&lt;b&gt;&lt;i&gt;Background/Aims:&lt;/i&gt;&lt;/b&gt; Gentamicin pharmacokinetics have not been described in patients undergoing short-daily hemodialysis (SDHD). The aim of this study is to describe gentamicin pharmacokinetics and dialytic clearance (Cl&lt;sub&gt;dial&lt;/sub&gt;) in SDHD patients and simulate gentamicin exposure after six dosing regimens to help guide future dosing. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Six anuric patients undergoing SDHD were enrolled. Patients received intravenous infusion of 2 mg/kg gentamicin on day 1 after the first HD session followed by HD sessions on days 2, 3, and 4. Blood samples for determination of gentamicin concentrations were serially collected. Gentamicin pharmacokinetic parameters and Cl&lt;sub&gt;dial&lt;/sub&gt; and interindividual variability terms (IIV) were estimated using NONMEM VII. Influence of patient weight on systemic clearance (Cl&lt;sub&gt;s&lt;/sub&gt;) and central volume of distribution (V&lt;sub&gt;c&lt;/sub&gt;) and influence of urea removal estimates on Cl&lt;sub&gt;dial&lt;/sub&gt; were assessed. The model was used to simulate gentamicin concentrations after six dosing regimens including pre- and postdialysis as well as daily and every-other-day dosing. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; A two-compartment model with first-order elimination from central compartment described gentamicin pharmacokinetics. Population estimates for Cl&lt;sub&gt;s&lt;/sub&gt; and Cl&lt;sub&gt;dial&lt;/sub&gt; were 7.6 and 134 ml/min, respectively. Patient weight was statistically significantly associated with Cl&lt;sub&gt;s&lt;/sub&gt; and V&lt;sub&gt;c&lt;/sub&gt;. Predialysis every-other-day regimens were as effective (C&lt;sub&gt;max&lt;/sub&gt; ≥8 mg/l and AUC&lt;sub&gt;48 h&lt;/sub&gt; ≥140 mg·h/l) and less toxic (C&lt;sub&gt;min&lt;/sub&gt; &lt;2 mg/l and AUC&lt;sub&gt;48 h&lt;/sub&gt; &lt;240 mg·h/l) than postdialysis regimens. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Estimated gentamicin Cl&lt;sub&gt;dial&lt;/sub&gt; is higher than previous estimates with thrice-weekly regimens. Predialysis every-other-day dosing may be recommended during SDHD.</jats:p

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American Journal of Nephrology

Gentamicin Pharmacokinetics and Pharmacodynamics during Short-Daily Hemodialysis

Gentamicin Pharmacokinetics and Pharmacodynamics during Short-Daily Hemodialysis

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