Pharmacokinetics of fentanyl in epileptic patients during concomitant therapy with phenytoin or carbamazepine
Ma, Zhijun.
2018
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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 dru... read moregs 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.read less - ID:
- v405sn81x
- Component ID:
- tufts:26069
- To Cite:
- DCA Citation Guide EndNote
