Incremental research approach to describing the pharmacokinetics of ciprofloxacin during extracorporeal membrane oxygenation
Background: Significant interactions between drugs, extracorporeal membrane oxygenation (ECMO) circuits and critical illness may affect the pharmacokinetic properties of antibiotics in critically ill patients receiving ECMO. Objective: To describe the pharmacokinetic properties of ciprofloxacin...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English English |
| Published: |
College of Intensive Care Medicine (CICM)
2017
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| Subjects: | |
| Online Access: | http://irep.iium.edu.my/59172/ http://irep.iium.edu.my/59172/ http://irep.iium.edu.my/59172/1/CCR_Sinnah_OctSupp17_1pp_auth_prf.pdf http://irep.iium.edu.my/59172/7/59172_Incremental%20research%20approach%20to%20describing%20the%20pharmacokinetics_scopus.pdf |
| Summary: | Background: Significant interactions between drugs,
extracorporeal membrane oxygenation (ECMO) circuits and
critical illness may affect the pharmacokinetic properties of
antibiotics in critically ill patients receiving ECMO.
Objective: To describe the pharmacokinetic properties
of ciprofloxacin during ECMO by integrating pre-clinical
findings (ie, ex vivo and in vivo ovine models) to a critically
ill patient.
Design, participants and intervention: An ex
vivo model of an ECMO circuit was used to describe
ciprofloxacin concentration changes over 24 hours. An
in vivo ovine model of ECMO was used to describe the
population pharmacokinetic properties of ciprofloxacin in
three different groups of sheep, and to investigate sources
of pharmacokinetic variability. In the final phase, data from
a 39-year-old critically ill man was used to validate the
findings from the ovine pharmacokinetic model.
Results: In the ex vivo model of ECMO circuits, the median
concentrations of ciprofloxacin at baseline and at 24 hours
after ciprofloxacin infusion were similar. The time course
of ciprofloxacin in the in vivo ovine on ECMO model was
adequately described by a two-compartment model. The
final population primary parameter mean estimates were:
clearance (CL), 0.21 L/kg/h (SD, 0.09 L/kg/h) and volume of
distribution (Vd
), 0.84 L/kg (SD, 0.12 L/kg). In the critically
ill ECMO patient, the primary pharmacokinetic parameter
estimates were: CL, 0.15 L/kg/h and Vd
, 0.99 L/kg.
Conclusions: We provide preliminary evidence that
ciprofloxacin dosing in ECMO patients should remain in
line with the recommended dosing strategies for critically ill
patients not receiving ECMO. |
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