Pharmacokinetics of fentanyl in epileptic patients during concomitant therapy with phenytoin or carbamazepine
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 ... read moredrugs 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
Thesis (M.S.)--Tufts University, 2018.
Submitted to the Dept. of Pharmacology and Drug Development.
Advisor: David Greenblatt.
Keywords: Pharmacology, and Pharmaceutical sciences.read less