%0 PDF %T Pharmacokinetics of fentanyl in epileptic patients during concomitant therapy with phenytoin or carbamazepine %A Ma, Zhijun. %D 2018-07-10T12:03:44.01-04:00 %8 2018-07-10 %R http://localhost/files/sb397m769 %X Abstract: Fentanyl was first approved for clinical use in the United States in 1968, and is an opioid used for pain medication and anesthesia. Clinical studies have shown that epileptic patients treated chronically with certain antiepileptic drugs, including carbamazepine and phenytoin, have higher fentanyl requirements during maintenance of anesthesia. The hypothesis is that antiepileptic drugs induce the activity of cytochrome P450 enzymes, causing increased hepatic clearance of fentanyl in epileptic patients. To characterize weather the pharmacokinetic of fentanyl are altered in patients receiving carbamazepine, 19 patients were recruited in this study. 11 patients were treated with carbamazepine based on their needs, and 8 patients served as controls. All patients received 200 mcg of fentanyl as a single bolus at anesthesia induction. Blood samples were collected at various time points for up to 9 hours. After liquid-liquid extraction by methyl tert-butyl ether, fentanyl concentrations in plasma samples were determined by UPLC-MS/MS. Concentration-time curves were fitted to a 2- compartment model or 3-compartment model. Statistical analysis showed that mean fentanyl clearance was higher in patients receiving carbamazepine (20.1 mL/kg/min vs 13.2 mL/kg/min). We did not measure hepatic blood flow in this study but hepatic blood flow is known to be measured by enzyme-inducing drugs. Therefore the increased clearance of fentanyl in carbamazepine-treated patients is likely attributable to induction of hepatic drug-metabolizing enzyme activity together with an increase in hepatic blood flow.; Thesis (M.S.)--Tufts University, 2018.; Submitted to the Dept. of Pharmacology and Drug Development.; Advisor: David Greenblatt.; Keywords: Pharmacology, and Pharmaceutical sciences. %[ 2022-10-12 %~ Tufts Digital Library %W Institution