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Urea kinetics and dialysis treatment time predict vancomycin elimination during high‐flux hemodialysis
Author(s) -
Schaedeli Franziska,
Uehlinger Dominik E.
Publication year - 1998
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(98)90118-7
Subject(s) - vancomycin , hemodialysis , dialysis , kinetics , urea , medicine , flux (metallurgy) , intensive care medicine , chemistry , biochemistry , biology , staphylococcus aureus , bacteria , genetics , physics , organic chemistry , quantum mechanics
Background Hemodialysis sessions with high‐flux filters ask for a reconsideration of the kinetics of xenobiotics. The aim of this study was to analyze whether individual high‐flux hemodialysis treatment parameters are of predictive value for dosing guidelines, with use of vancomycin as a model compound. Methods Twenty‐six patients receiving high‐flux hemodialysis were studied prospectively. After an intravenous infusion of 1000 mg or 500 mg vancomycin, respectively, six to eight blood samples were collected within a period of 5 to 9 days, including one hemodialysis session. Serum vancomycin concentrations were measured by HPLC. Nonlinear mixed‐effects modeling (NONMEM) was used to fit a two‐compartment population pharmacokinetic model to the data of 20 patients; the data of the remaining six patients (group II) were used for a prospective evaluation of the model. Results A linear relationship was found between vancomycin filter clearance (CLD V ) and urea filter clearance (CLD BUN ), derived from Kt/V (the product of urea clearance [K] and dialysis treatment time [t], standardized for the urea volume of distribution [V]). Mean (coefficient of variation) steady‐state volume of distribution was 1.05 L/kg (22%), CLD V was 0.336 · CLD BUN (13%), and residual interdialytic clearance was 2.25 ml/min (90%) in patients with creatinine clearance values (CL CR ) below 2 ml/min and 2.25 ml/min + 0.59 · CL CR (32%) in patients with CL CR values above 2 ml/min. The model predicted predialysis vancomycin concentrations before the first and the second postinfusion dialysis session in the six patients of group II, with a deviation of 1.8 ± 1.0 mg/L and 0.8 ± 0.5 mg/L, respectively. Conclusion The described population pharmacokinetic model allows individualization of vancomycin dosing intervals in patients receiving hemodialysis, based on patient characteristics and urea kinetic modeling. Clinical Pharmacology & Therapeutics (1998) 63 , 26–38; doi: