title: Effect of memantine on plasma concentrations of carbamazepine and phenytoin in rats: A controlled experimental study.
abstract: BACKGROUND
  Elderly patients, especially those with Alzheimer's disease, may be prescribed memantine and an antiepileptic drug concurrently.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Memantine was not associated with a significant change in the plasma concentration of CBZ, CBZE, or phenytoin in this experimental model.
authors.affiliation: Faculty of Specialized Veterinary Science, Islamic Azad University, Science & Research Branch, Tehran, Iran.
authors.forename: Amir Reza Karami
authors.initials: AR
authors.lastname: Bonary
authors.affiliation: Pharmacy and Drug Applied Research Center, Tabriz University (Medical Sciences), Tabriz, Iran.
authors.forename: Abolghasem
authors.initials: A
authors.lastname: Jouyban
authors.affiliation: Biotechnology Research Center, Tabriz University (Medical Sciences), Tabriz, Iran.
authors.forename: Elnaz
authors.initials: E
authors.lastname: Tamizi
authors.affiliation: Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shahram Ejtemaei
authors.initials: SE
authors.lastname: Mehr
authors.affiliation: Faculty of Specialized Veterinary Science, Islamic Azad University, Science & Research Branch, Tehran, Iran ; Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Samini
keywords: Alzheimer's disease; carbamazepine; epilepsy; memantine; phenytoin; rat