Pharmacodynamic and pharmacokinetic interaction of Panchagavya Ghrita with phenytoin and carbamazepine in maximal electroshock induced seizures in rats

INTRODUCTION: Traditionally, Panchagavya Ghrita (PG) has been used for the management of epilepsy, anxiety, fever and jaundice. It consists of five components of cow products namely, cow milk, clarified butter from cow milk, cow urine, curd from cow milk, and cow dung juice. AIM: To evaluate the effect of PG in maximal electroshock (MES) induced seizures model and its pharmacodynamic and pharmacokinetic interaction with phenytoin (PHT) and carbamazepine (CBZ) in rats. MATERIALS AND METHODS: Male Wistar rats were administered PG 500, 1000, 2000, and 4000 mg/kg orally for 7 days and seizures were induced by MES. For interaction studies, PG (4000 mg/kg) was administered along with a sub-therapeutic dose of PHT (20 mg/kg, p.o.) and CBZ (10 mg/kg, p.o.). Behavioral parameters were assessed. Oxidative stress markers and serum levels of PHT and CBZ were estimated. RESULTS: Tonic hind limb extension, cognitive impairment, and oxidative stress produced by MES were reversed by PG (4000 mg/kg). Co-administration of PG (4000 mg/kg) with a sub-therapeutic dose of PHT and CBZ potentiated antiepileptic effect and ameliorated cognitive impairment as well as oxidative stress. Although, there was a slight increase in serum levels of PHT and CBZ on co-administration with PG, it was statistically insignificant. CONCLUSION: Co-administration of PG with low doses of PHT and CBZ caused complete seizure protection. This suggests the potential of PG as an adjunct in epilepsy with improved efficacy and tolerability.