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Pharmacokinetics and pharmacodynamics of propofol in children undergoing different types of surgeries |
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| Institution: | 1. Department of Pediatric Anesthesiology and Intensive Therapy, Poznań University of Medical Sciences, Poznań, Poland;2. Department of Clinical Pharmacy and Biopharmacy, Poznań University of Medical Sciences, Poznań, Poland;3. Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gdańsk, Poland;4. Department of Anaesthesiology and Intensive Therapy, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland;5. Department of Teaching Anesthesiology and Intensive Therapy, Poznań University of Medical Sciences, Poznań, Poland;6. Department of Analytical Chemistry, Poznan University of Medical Sciences, Poznań, Poland;1. Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University, Medical College, Krakow, Poland;2. Chair of Pharmacobiology, Jagiellonian University, Medical College, Krakow, Poland;3. Chair of Pharmaceutical Chemistry, Department of Physicochemical Drug Analysis, Jagiellonian University, Medical College, Krakow, Poland;4. Chair of Pharmacodynamics, Jagiellonian University, Medical College, Krakow, Poland;5. Laboratory of Trace Elements Neurobiology, Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences and Center of Excellence in Neuropsychopharmacology, Krakow, Poland;1. Department of Histology, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina;2. School of Science and Technology, National University of San Martin, Buenos Aires, Argentina;3. Department of Physiology, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina;4. Department of Biochemistry, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina;1. Jiangnan University, Wuxi 214122, China;2. Kingstone Semiconductor Co., Ltd, Shanghai 201203, China;3. Suntech Power Co., Ltd, Wuxi 214028, China;4. Jiangsu (Suntech) Institute for Photovoltaic Technology, Wuxi 214028, China |
| Abstract: | BackgroundPropofol is a commonly used agent in total intravenous anesthesia (TIVA). However, the link between its pharmacokinetics and pharmacodynamics has not been fully characterized in children yet. Our aim was to determine the quantitative relationship between the venous plasma concentration and bispectral index (BIS) effect in a heterogeneous group of pediatric patients undergoing various surgical procedures (ASA status I–III).MethodsNine male and nine female patients were anesthetized with propofol–fentanyl TIVA. Sparse venous samples for propofol concentrations assay and dense BIS measurements were collected during and after the end of infusion. Nonlinear mixed-effect modeling in NONMEM was used for data analysis.ResultsA three-compartment model was linked with a classical Emax model through a biophase compartment to describe the available data. All clearance and volume terms were allometrically scaled to account for the body mass difference among the patients under study. A typical patient had their PK parameters observed within the range of literature values for children. The pharmacodynamic parameters were highly variable. The EC50 of 2.80 mg/L and the biophase distribution rate constant of 3.33 min?1 were found for a typical patient.ConclusionsThe BIS values in children are highly correlated with the propofol effect compartment concentrations according to the classical Emax concentration–response relationship. Children had slightly lower sensitivity to propofol and slightly higher clearance, as compared with the adult data available in literature. The intra-patient variations in the BIS require the anesthesiologist's attention in using BIS values alone to evaluate the depth of anesthesia in children. |
| Keywords: | Propofol Bispectral index Pharmacokinetic and pharmacodynamics modeling Children Total intravenous anesthesia |
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