Antimicrobial Agents and Chemotherapy · 2012 · 81 citations · 7 references
PharmacyClinical PharmacokineticsPharmacokineticsAntimicrobial PharmacotherapyClinical PharmacologyDrug ClearancePharmacokinetics In Critical IllnessPharmacokinetics Of AntimicrobialsArea Under The Concentration - Time CurveArea Under The Plasma Concentration-time CurveColistin DosingCritically Ill Patient Drug ClearanceDosage Regimen OptimizationFraction Unbound DrugPharmacokinetic ParametersUnbound Fraction
This report describes the pharmacokinetics of colistin methanesulfonate (CMS) and colistin in five intensive care unit patients receiving continuous venovenous hemodiafiltration. For CMS, the mean maximum concentration of drug in plasma (C(max)) after the fourth dose was 6.92 mg/liter and total clearance (CL) 8.23 liters/h. For colistin, the mean concentration was 0.92 mg/liter and CL/metabolized fraction (f(m)) 18.91 liters/h. Colistin concentrations were below the current MIC breakpoints, and the area under the concentration-time curve for the free, unbound fraction of the drug over 24 h in the steady state divided by the MIC (fAUC/MIC) was lower than recommended, suggesting that a dosage regimen of 160 mg CMS every 8 h (q8h) is inadequate.
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