Ciprofloxacin in Patients Undergoing Extracorporeal Membrane Oxygenation (ECMO): A Population Pharmacokinetic Study
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Ciprofloxacin in Patients Undergoing Extracorporeal Membrane Oxygenation (ECMO): A Population Pharmacokinetic Study. / Alihodzic, Dzenefa; Wicha, Sebastian G.; Frey, Otto R.; König, Christina; Baehr, Michael; Jarczak, Dominik; Kluge, Stefan; Langebrake, Claudia.
In: PHARMACEUTICS, Vol. 14, No. 5, 965, 29.04.2022.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -