title: Pharmacokinetics and pharmacodynamics of propofol and fentanyl in patients undergoing abdominal aortic surgery - a study of pharmacodynamic drug-drug interactions.
abstract: Propofol is routinely combined with opioid analgesics to ensure adequate anesthesia during surgery. The aim of the study was to assess the effect of fentanyl on the hypnotic effect of propofol and the possible clinical implications of this interaction. The pharmacokinetic/pharmacodynamic (PK/PD) data were obtained from 11 patients undergoing abdominal aortic surgery, classified as ASA III. Propofol was administered by a target-controlled infusion system. Fentanyl 2-3 µg/kg was given whenever insufficient analgesia occurred. The bispectral index (BIS) was used to monitor the depth of anesthesia. A population PK/PD analysis with a non-linear mixed-effect model (NONMEM 7.2 software) was conducted. Two-compartment models satisfactorily described the PK of propofol and fentanyl. The delay of the anesthetic effect in relation to PK was described by the effect compartment. The BIS was linked to propofol and fentanyl effect-site concentrations through an additive Emax model. Context-sensitive decrement times (CSDT) determined from the final model were used to assess the influence of fentanyl on the recovery after anesthesia. The population PK/PD model was successfully developed to describe simultaneously the time course and variability of propofol and fentanyl concentrations and BIS. Additive propofol-fentanyl interactions were observed and quantitated. The duration of the fentanyl infusion had minimal effect on CSDT when it was shorter than the duration of the propofol infusion. If the fentanyl infusion was longer than the propofol infusion, an almost two-fold increase in CSDT occurred. Additional doses of fentanyl administered after the cessation of the propofol infusion result in lower BIS values, and can prolong the time of recovery from anesthesia. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Poland.
authors.forename: Paweł
authors.identifier: http://orcid.org/0000-0002-2878-3161
authors.initials: P
authors.lastname: Wiczling
authors.affiliation: Department of Anesthesiology and Intensive Therapy, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Bieda
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Przybyłowski
authors.affiliation: Department of Experimental Anesthesiology, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
authors.forename: Roma
authors.initials: R
authors.lastname: Hartmann-Sobczyńska
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Borsuk
authors.affiliation: Department of Inorganic and Analytical Chemistry, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Matysiak
authors.affiliation: Department of Inorganic and Analytical Chemistry, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
authors.forename: Zenon J
authors.initials: ZJ
authors.lastname: Kokot
authors.affiliation: Department of Anesthesiology and Intensive Therapy, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Sobczyński
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
authors.forename: Edmund
authors.initials: E
authors.lastname: Grześkowiak
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bienert
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000493:pharmacokinetics / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000493:pharmacokinetics / Q000494:pharmacology; D001012:Aorta, Abdominal / Q000601:surgery; D004347:Drug Interactions; D005283:Fentanyl / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics / Q000494:pharmacology; D008875:Middle Aged; D008954:Models, Biological; D015742:Propofol / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000701:Analgesics, Opioid; D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D005283:Fentanyl; D015742:Propofol
keywords: PK/PD; abdominal aortic surgery; fentanyl; propofol