Prolonged therapy with the anticonvulsant carbamazepine leads to increased plasma clearance of fentanyl.

The Journal of Pharmacy and Pharmacology
Ala NozariJ A Jeevendra Martyn

Abstract

Fentanyl is a potent analgesic that accounts for an increasing number of overdose deaths in the United States. This study tested whether altered pharmacokinetics plays a pivotal role in the increased fentanyl dose requirements in patients receiving the enzyme-inducing anticonvulsant, carbamazepine. Neurosurgical patients receiving carbamazepine for >6 weeks (N = 11) or no carbamazepine (N = 6, controls) received a single bolus dose of fentanyl (200 μg) intravenously. Plasma was collected before and for up to 9 h after the bolus. Fentanyl concentrations were measured using liquid chromatography-mass spectrometry. Pharmacokinetic variables were derived from plasma concentration-time curves best fitted to a two-compartment model. Fentanyl clearance was significantly higher in the carbamazepine group compared to controls (mean ± SD: 20.1 ± 6.8 vs 13.2 ± 4.8 ml/min per kg, P < 0.05), and area under the plasma concentration curve (AUC) was significantly lower (150 ± 65 vs 233 ± 70 ng/ml × min, P < 0.02). Volume of distribution was larger in the carbamazepine group, but the difference was not statistically significant (5.4 ± 3.1 vs 3.6 ± 1.2 l/kg, P > 0.15). The terminal elimination half-life did not differ between the two groups. Chr...Continue Reading

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Citations

Mar 18, 2021·Translational Research : the Journal of Laboratory and Clinical Medicine·Joseph B O'Brien, David L Roman
Aug 20, 2021·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Sara ShumNina Isoherranen

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