Population pharmacokinetics of ciprofloxacin in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study)

• DOI: 10.1016/j.accpm.2022.101080
• Publication Date: 2022-04-25T08:34:16Z
• Authors: Vesa Cheng; Mohd H. Abdul-Aziz; Fay Burrows; Hergen Buscher; Amanda Corley; Arne Diehl; Bianca J. Levkovich; Vincent Pellegrino; Claire Reynolds; Sam Rudham; Steven C. Wallis; Susan A. Welch; Jason A. Roberts; Kiran Shekar; John F. Fraser
• Keywords: Regimen; Therapeutic Drug Monitoring; Body surface area; Renal replacement therapy

This study aimed to describe the pharmacokinetics (PK) of ciprofloxacin in critically ill patients receiving ECMO and recommend a dosing regimen that provides adequate drug exposure.Serial blood samples were taken from ECMO patients receiving ciprofloxacin. Total ciprofloxacin concentrations were measured by chromatographic assay and analysed using a population PK approach with Pmetrics®. Dosing simulations were performed to ascertain the probability of target attainment (PTA) represented by the area under the curve to minimum inhibitory concentration ratio (AUC0-24/MIC) ≥ 125.Eight patients were enrolled, of which three received concurrent continuous venovenous haemodiafiltration (CVVHDF). Ciprofloxacin was best described in a two-compartment model with total body weight and creatinine clearance (CrCL) included as significant predictors of PK. Patients not requiring renal replacement therapy generated a mean clearance of 11.08 L/h while patients receiving CVVHDF had a mean clearance of 1.51 L/h. Central and peripheral volume of distribution was 77.31 L and 90.71 L, respectively. ECMO variables were not found to be significant predictors of ciprofloxacin PK. Dosing simulations reported that a 400 mg 8 -hly regimen achieved > 72% PTA in all simulated patients with CrCL of 30 mL/min, 50 mL/min and 100 mL/min and total body weights of 60 kg and 100 kg at a MIC of 0.5 mg/L.Our study reports that established dosing recommendations for critically ill patients not on ECMO provides sufficient drug exposure for maximal ciprofloxacin activity for ECMO patients. In line with non-ECMO critically ill adult PK studies, higher doses and therapeutic drug monitoring may be required for critically ill adult patients on ECMO.