Pawel Wiczling (1), Krzysztof Bieda (3) Agnieszka Bienert (2), Krzysztof Przybylowski (2), Martyna Józefowicz (1), Pawel Sobczynski (3), Roma Hartmann-Sobczynska (4), Roman Kaliszan (1), Edmund Grzeskowiak (2)
(1) Department of Biopharmaceutics and Pharmacokinetics, Medical University of Gdansk, Poland; (2) Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences; (3) Department of Anaesthesiology and Intensive Therapy, Poznan University of Medical Sciences, (4) Department of Experimental Anaesthesiology, Poznan University of Medical Sciences, Poland
Objectives: Pharmacokinetic (PK) and pharmacodynamic (PD) data of propofol and fentanyl, the cardiac output (CO) measurements, and the bispectral index (BIS) were available from a study of ASA physical status III patients scheduled for abdominal aortic surgery. The aim of the work was to assess the influence of cardiac output on propofol and fentanyl PK/PD and to determine the effect of fentanyl on hypnotic effects of propofol.
Methods: After institutional approval, the data was obtained from ten patients of 50 to 75 years age and weighing between 50 and 92 kg. Propofol was administered by means of the target-controlled infusion system (Diprifusor) and fentanyl was given whenever inadequate analgesia was assessed throughout the surgery at a dose of 2–3 µg/kg. Hemodynamic measurements were done with FloTrac/Vigileo TM (Edwards, USA). The bispectral index (BIS) served to monitor the depth of anesthesia and was kept between 40 and 60. PK/PD analysis was performed by using a non-linear mixed-effect population model (NONMEM 7.2 software).
Results: A three and a two compartment model was sufficient to describe propofol and fentanyl PK. The delay of the anesthetic effect, with respect to plasma concentrations, was described by the effect compartment. The BIS index was linked to the propofol and fentanyl effect site concentrations through a synergistic Emax model. In this study the cardiac output has been identified as significant covariant influencing fentanyl disposition (elimination and distribution clearance). The effects of CO on propofol PK were less evident and could not be supported by the present data.
Conclusions: The population PK/PD model was successfully developed to describe the time course and variability of propofol and fentanyl concentrations and BIS index. The effects of CO on fentanyl PK and interactions between fentanyl and propofol were observed in the study.
Reference: PAGE 23 () Abstr 3183 [www.page-meeting.org/?abstract=3183]
Poster: Drug/Disease modeling - Other topics