Ciprofloxacin in Patients Undergoing Extracorporeal Membrane Oxygenation (ECMO): A Population Pharmacokinetic Study

TY - JOUR

T1 - Ciprofloxacin in Patients Undergoing Extracorporeal Membrane Oxygenation (ECMO): A Population Pharmacokinetic Study

AU - Alihodzic, Dzenefa

AU - Wicha, Sebastian G.

AU - Frey, Otto R.

AU - König, Christina

AU - Baehr, Michael

AU - Jarczak, Dominik

AU - Kluge, Stefan

AU - Langebrake, Claudia

PY - 2022/4/29

Y1 - 2022/4/29

N2 - Extracorporeal membrane oxygenation (ECMO) is utilized to temporarily sustain respiratory and/or cardiac function in critically ill patients. Ciprofloxacin is used to treat nosocomial infections, but data describing the effect of ECMO on its pharmacokinetics is lacking. Therefore, a prospective, observational trial including critically ill adults (n = 17), treated with ciprofloxacin (400 mg 8-12 hourly) during ECMO, was performed. Serial blood samples were collected to determine ciprofloxacin concentrations to assess their pharmacokinetics. The pharmacometric modeling was performed (NONMEM®) and utilized for simulations to evaluate the probability of target attainment (PTA) to achieve an AUC0-24/MIC of 125 mg·h/L for ciprofloxacin. A two-compartment model most adequately described the concentration-time data of ciprofloxacin. Significant covariates on ciprofloxacin clearance (CL) were plasma bicarbonate and the estimated glomerular filtration rate (eGFR). For pathogens with an MIC of ≤0.25 mg/L, a PTA of ≥90% was attained. However, for pathogens with an MIC of ≥0.5 mg/L, plasma bicarbonate ≥ 22 mmol/L or eGFR ≥ 10 mL/min PTA decreased below 90%, steadily declining to 7.3% (plasma bicarbonate 39 mmol/L) and 21.4% (eGFR 150 mL/min), respectively. To reach PTAs of ≥90% for pathogens with MICs ≥ 0.5 mg/L, optimized dosing regimens may be required.

AB - Extracorporeal membrane oxygenation (ECMO) is utilized to temporarily sustain respiratory and/or cardiac function in critically ill patients. Ciprofloxacin is used to treat nosocomial infections, but data describing the effect of ECMO on its pharmacokinetics is lacking. Therefore, a prospective, observational trial including critically ill adults (n = 17), treated with ciprofloxacin (400 mg 8-12 hourly) during ECMO, was performed. Serial blood samples were collected to determine ciprofloxacin concentrations to assess their pharmacokinetics. The pharmacometric modeling was performed (NONMEM®) and utilized for simulations to evaluate the probability of target attainment (PTA) to achieve an AUC0-24/MIC of 125 mg·h/L for ciprofloxacin. A two-compartment model most adequately described the concentration-time data of ciprofloxacin. Significant covariates on ciprofloxacin clearance (CL) were plasma bicarbonate and the estimated glomerular filtration rate (eGFR). For pathogens with an MIC of ≤0.25 mg/L, a PTA of ≥90% was attained. However, for pathogens with an MIC of ≥0.5 mg/L, plasma bicarbonate ≥ 22 mmol/L or eGFR ≥ 10 mL/min PTA decreased below 90%, steadily declining to 7.3% (plasma bicarbonate 39 mmol/L) and 21.4% (eGFR 150 mL/min), respectively. To reach PTAs of ≥90% for pathogens with MICs ≥ 0.5 mg/L, optimized dosing regimens may be required.

U2 - 10.3390/pharmaceutics14050965

DO - 10.3390/pharmaceutics14050965

M3 - SCORING: Journal article

C2 - 35631551

VL - 14

JO - PHARMACEUTICS

JF - PHARMACEUTICS

SN - 1999-4923

IS - 5

M1 - 965

ER -