Abstract

ANTICONVULSANT ACTIVITY OF DIVALPROEX SODIUM AND EFFECT OF GLIMEPIRIDE ON PHARMACOKINETIC: AN EXPERIMENTAL DRUG INTERACTION STUDY

Author(s): SHYAM SHAH1, SATYAM PRAKASH*2, RAKESH KUMAR YADAV3, KHUSHBU YADAV4, N.C. NAGALAKSHMI

Background  and  Objectives:Epilepsy  is  a  serious  and  common  chronic  neurological  disorder  caused  by  abnormal  synchronized  neuronal  discharges.  Divalproex  is suggested to increase GABA concentration in brain. Both Divalproex and Glimepiride used for long duration indicate for CNS disorder and Diabetes mellitus. The study was conducted to find the influence of Glimepiride on pharmacokinetic and anticonvulsant activity of Divalproex.Methods:Four healthy rabbits of either sex were used to study the effect  of  Glimepiride  on  pharmacokinetic  parameters  of  Divalproex.  The  concentration  of  Valproic  acid  (VPA)  in  serum  was  estimated  by  HPLC  coupled  with  Mass Spectroscopy (LC-MS/MS). Anticonvulsant activity was studied using Maximal Electroshock (MES) method and Pentylenetetrazole (PTZ) test in healthy albino rats.Results: The  serum  concentration  of  VPA  was  significantly  increased  after  Glimepiride  treatment  for  7  days.  Pharmacokinetic  parameterslike  AUC,  AUMC,  T1/2and  Cmaxof  VPA showed significant change after Glimepiride treatment in healthy albino rabbits. Glimepiride also exhibited significant increase in duration of hind limb extensor time and onset of  clonic  convulsion  time  in  MES  and  PTZ  induced  seizure  test  respectively.  The  percentage  prolongation  of  onset  of  clonic  convulsion  was  decreased  to  49.6%  in combination treatment. Conclusion: The drug-drug interaction between Divalproex and Glimepiride could be due to metabolism of both the drugs at the same site and proteinbinding to albumin

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ISSN: 2320-3315

ICV :81.58

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