caa a22 4500 605534225 CHVBK 20210128100841.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s10928-015-9404-6 doi (NATIONALLICENCE)springer-10.1007/s10928-015-9404-6 Pharmacokinetics and pharmacodynamics of propofol in cancer patients undergoing major lung surgery [Elektronische Daten] [Krzysztof Przybyłowski, Joanna Tyczka, Damian Szczesny, Agnieszka Bienert, Paweł Wiczling, Katarzyna Kut, Emilia Plenzler, Roman Kaliszan, Edmund Grześkowiak] Despite the growing number of cancer cases and cancer surgeries around the world, the pharmacokinetics (PK) and pharmacodynamics (PD) of anesthetics used in this population are poorly understood. Patients operated due to cancer are usually in severe state and often require chemotherapy. It might affect the PK/PD of drugs used in this population. Therefore,inthisstudy we explored the PK/PD of propofol in cancer patients having a major lung surgery. 23 patients that underwent a propofol-fentanyl total intravenous anesthesia were included in the analysis. A large set of demographic, biochemical and hemodynamic parameters was collected for the purpose of covariate analysis. Nonlinear mixed effect modeling in NONMEM was used to analyze the collected data. A three-compartment model was sufficient to describe PK of propofol. The anesthetic effect (AAI index) was linked to the propofol effect site concentrations through a sigmoidal E max model. A slightly higher value of clearance, a lower value of distribution clearance, and a decreased volume of peripheral compartment were observed in our patients, as compared with the literature values reported for healthy volunteers by Schnider et al. and by Eleveld et al. Despite these differences, both models led to a clinically insignificant bias of −8 and −1% in concentration predictions, as reflected by the median performance error. The C e50 and propofol biophase concentration at the time of postoperative orientation were low and equaled 1.40 and 1.13mg/L. The population PK/PD model was proposed for cancer patients undergoing a major lung surgery. The large body of studied covariates did not affect PK/PD of propofol significantly. The modification of propofol dosage in the group of patients under study is not necessary when TCI-guided administration of propofol by means of the Schnider model is used. The Author(s), 2015 Propofol nationallicence PK/PD nationallicence AAI index nationallicence Cancer patients nationallicence Major lung surgery nationallicence Przybyłowski Krzysztof Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Poznan, Poland aut Tyczka Joanna Intensive Care Department, Pulmonary Diseases and Thoracic Surgery Center, Poznan, Poland aut Szczesny Damian Department of Biopharmaceutics and Pharmacokinetics, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416, Gdańsk, Poland aut Bienert Agnieszka Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Poznan, Poland aut Wiczling Paweł Department of Biopharmaceutics and Pharmacokinetics, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416, Gdańsk, Poland aut Kut Katarzyna Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Poznan, Poland aut Plenzler Emilia Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Poznan, Poland aut Kaliszan Roman Department of Biopharmaceutics and Pharmacokinetics, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416, Gdańsk, Poland aut Grześkowiak Edmund Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Poznan, Poland aut Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/2(2015-04-01), 111-122 1567-567X 42:2<111 2015 42 10928 https://doi.org/10.1007/s10928-015-9404-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10928-015-9404-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Przybyłowski Krzysztof Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Poznan, Poland aut NATIONALLICENCE 700 1- Tyczka Joanna Intensive Care Department, Pulmonary Diseases and Thoracic Surgery Center, Poznan, Poland aut NATIONALLICENCE 700 1- Szczesny Damian Department of Biopharmaceutics and Pharmacokinetics, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416, Gdańsk, Poland aut NATIONALLICENCE 700 1- Bienert Agnieszka Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Poznan, Poland aut NATIONALLICENCE 700 1- Wiczling Paweł Department of Biopharmaceutics and Pharmacokinetics, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416, Gdańsk, Poland aut NATIONALLICENCE 700 1- Kut Katarzyna Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Poznan, Poland aut NATIONALLICENCE 700 1- Plenzler Emilia Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Poznan, Poland aut NATIONALLICENCE 700 1- Kaliszan Roman Department of Biopharmaceutics and Pharmacokinetics, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416, Gdańsk, Poland aut NATIONALLICENCE 700 1- Grześkowiak Edmund Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Poznan, Poland aut NATIONALLICENCE 773 0- Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/2(2015-04-01), 111-122 1567-567X 42:2<111 2015 42 10928