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

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Cheng, V
Abdul-Aziz, MH
Burrows, F
Buscher, H
Corley, A
Diehl, A
Levkovich, BJ
Pellegrino, V
Reynolds, C
Rudham, S
Wallis, SC
Welch, SA
Roberts, JA
Shekar, K
Fraser, JF
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2022
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Abstract

Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.

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Anaesthesia Critical Care & Pain Medicine

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41

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3

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Subject

Anaesthesiology

Antibiotics

Continuous renal replacement therapy

Dosing

Extracorporeal membrane oxygenation

Fluoroquinolone

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Cheng, V; Abdul-Aziz, MH; Burrows, F; Buscher, H; Corley, A; Diehl, A; Levkovich, BJ; Pellegrino, V; Reynolds, C; Rudham, S; Wallis, SC; Welch, SA; Roberts, JA; Shekar, K; Fraser, JF, Population pharmacokinetics of ciprofloxacin in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study), Anaesthesia Critical Care & Pain Medicine, 2022, 41 (3), pp. 101080

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