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Increased carbamazepine plasma concentrations after fluoxetine coadministration
S R Grimsley1, M W Jann, J G Carter
1Department of Pharmacy Practice, Mercer University School of Pharmacy, Atlanta, GA 30312.
Clinical Pharmacology and Therapeutics
|July 1, 1991
Summary
Fluoxetine significantly increases carbamazepine levels by inhibiting its metabolism, as shown in healthy volunteers. This drug interaction necessitates careful patient monitoring when coadministering these medications.
Area of Science:
- Pharmacology
- Drug Metabolism
- Clinical Pharmacology
Background:
- Carbamazepine is an anticonvulsant and mood-stabilizing drug.
- Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) antidepressant.
- Potential drug interactions between carbamazepine and fluoxetine require investigation.
Purpose of the Study:
- To investigate the pharmacokinetic interaction between fluoxetine and carbamazepine.
- To determine if fluoxetine affects carbamazepine metabolism and clearance.
Main Methods:
- Six healthy male volunteers received carbamazepine for 3 weeks.
- Fluoxetine was coadministered with carbamazepine for 7 days.
- Carbamazepine and its epoxide metabolite (CBZE) levels were measured using HPLC.
Main Results:
- Fluoxetine significantly increased the area under the concentration-time curve (AUC) for both carbamazepine and CBZE.
- Oral and intrinsic clearance of carbamazepine were significantly decreased following fluoxetine addition.
- No significant changes in absorption or distribution parameters were observed.
Conclusions:
- Fluoxetine inhibits the metabolism of carbamazepine.
- This interaction can lead to increased carbamazepine exposure.
- Close patient monitoring is recommended when coadministering fluoxetine and carbamazepine.