Effect of memantine on plasma concentrations of carbamazepine and phenytoin in rats: A controlled experimental study

Elderly patients, especially those with Alzheimer's disease, may be prescribed memantine and an antiepileptic drug concurrently.

The aim of this study was to compare the interaction of memantine with phenobarbital (an enzyme inducer) and chloramphenicol (an enzyme inhibitor) on plasma concentrations of carbamazepine (CBZ), CBZ-10,11-epoxide (CBZE), and phenytoin in an experimental model.

Eight groups of rats (200-230 g) were treated for 14 days each. In groups 1 and 2, phenobarbital 50 mg/kg was administered daily as an enzyme inducer 60 minutes before CBZ 50 mg/kg or phenytoin 30 mg/kg administration, respectively. In groups 3 and 4, chloramphenicol 300 mg/kg was administered daily as an enzyme inhibitor 60 minutes before CBZ or phenytoin administration, respectively. In groups 5 and 6, memantine 20 mg/kg was administered daily 60 minutes before CBZ or phenytoin, respectively. In group 7, CBZ alone was administered daily; in group 8, phenytoin alone was administered daily. Two hours after the last intragastric gavage, animals were anesthetized with ether and 2 mL of blood was drawn from the heart into a syringe containing EDTA. A validated method developed in this study was used for simultaneous determination of CBZ, CBZE, and phenytoin concentrations in rat plasma.

The study comprised 8 groups of 9 male adult Wistar rats each. Compared with groups 7 and 8, concurrent use of CBZ or phenytoin with phenobarbital (groups 1 and 2) was associated with significantly lower mean (SEM) plasma concentrations of CBZ (3.45 [0.16] vs 2.20 [0.21] μg/mL; P < 0.001) and phenytoin (3.68 [0.09] vs 1.63 [0.15] μg/mL; P < 0.001) and a significantly higher plasma CBZE concentration (9.85 [0.29] vs 11.18 [0.29] μg/mL; P < 0.05). Concurrent use of CBZ or phenytoin with chloramphenicol (groups 3 and 4) was associated with significantly higher plasma concentrations of CBZ (4.81 [0.17] μg/mL; P < 0.001) and phenytoin (6.24 [0.22] μg/mL; P < 0.001) and a significantly lower plasma CBZE concentration (3.88 [0.25] μg/mL; P < 0.001). Concurrent use of CBZ or phenytoin with memantine (groups 5 and 6) was not associated with a significant change in the plasma concentration of CBZ, CBZE, or phenytoin.

Memantine was not associated with a significant change in the plasma concentration of CBZ, CBZE, or phenytoin in this experimental model.