Despite the growing number of cancer cases\nand cancer surgeries around the world, the pharmacokinetics\n(PK) and pharmacodynamics (PD) of anesthetics\nused in this population are poorly understood. Patients\noperated due to cancer are usually in severe state and often\nrequire chemotherapy. It might affect the PK/PD of drugs\nused in this population. Therefore, in this study we\nexplored the PK/PD of propofol in cancer patients having a\nmajor lung surgery. 23 patients that underwent a propofolââ?¬â??\nfentanyl total intravenous anesthesia were included in the\nanalysis. A large set of demographic, biochemical and\nhemodynamic parameters was collected for the purpose of\ncovariate analysis. Nonlinear mixed effect modeling in\nNONMEM was used to analyze the collected data. A threecompartment\nmodel was sufficient to describe PK of propofol.\nThe anesthetic effect (AAI index) was linked to the\npropofol effect site concentrations through a sigmoidal\nEmax model. A slightly higher value of clearance, a lower\nvalue of distribution clearance, and a decreased volume of\nperipheral compartment were observed in our patients, as\ncompared with the literature values reported for healthy\nvolunteers by Schnider et al. and by Eleveld et al. Despite\nthese differences, both models led to a clinically insignificant\nbias of -8 and -1 % in concentration predictions, as\nreflected by the median performance error. The Ce50 and\npropofol biophase concentration at the time of postoperative\norientation were low and equaled 1.40 and 1.13 mg/L.\nThe population PK/PD model was proposed for cancer\npatients undergoing a major lung surgery. The large body\nof studied covariates did not affect PK/PD of propofol\nsignificantly. The modification of propofol dosage in the\ngroup of patients under study is not necessary when TCIguided\nadministration of propofol by means of the Schnider\nmodel is used.
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