C Sharma1, R Dubey, H Kumar, N Saha. 1. Department of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences, New Delhi, India.
Abstract
BACKGROUND AND OBJECTIVE:Lamotrigine is a relatively newer antiepileptic drug used in the treatment of partial seizures. It has a narrow therapeutic index and hence the achieved blood level of the drug is closely related to the therapeutic efficacy and toxicity. The bioavailability of lamotrigine is affected by food, hence the present study was done to investigate the effect of two types of food on the bioavailability of lamotrigine. METHODS: A randomized, open-label, three treatment, three period, single dose and cross-over study was done in nine healthy male volunteers. A single dose of lamotrigine (100 mg) was administered at three occasions: after a north Indian diet (high calorie, high fat), after a south Indian diet (low calorie, low fat), and after an overnight fasting. Serial blood samples were collected up to 24 h post dose. Plasma lamotrigine concentrations were determined and pharmacokinetic parameters studied. RESULTS: A statistically significant decrease in rate and extent of absorption was observed with north Indian diet and south Indian diet when compared with fasting group. Presence of both types of food causes decrease in mean values of C(max), AUC((0-t)), and AUC((0-alpha)) thus reducing the bioavailability of lamotrigine at significant level (P<0.05). INTERPRETATION AND CONCLUSION:Lamotrigine should be taken preferably in fasting condition, as presence of food (low fat, low calorie or high fat, high calorie) decreases the bioavailability to a significant extent.
RCT Entities:
BACKGROUND AND OBJECTIVE:Lamotrigine is a relatively newer antiepileptic drug used in the treatment of partial seizures. It has a narrow therapeutic index and hence the achieved blood level of the drug is closely related to the therapeutic efficacy and toxicity. The bioavailability of lamotrigine is affected by food, hence the present study was done to investigate the effect of two types of food on the bioavailability of lamotrigine. METHODS: A randomized, open-label, three treatment, three period, single dose and cross-over study was done in nine healthy male volunteers. A single dose of lamotrigine (100 mg) was administered at three occasions: after a north Indian diet (high calorie, high fat), after a south Indian diet (low calorie, low fat), and after an overnight fasting. Serial blood samples were collected up to 24 h post dose. Plasma lamotrigine concentrations were determined and pharmacokinetic parameters studied. RESULTS: A statistically significant decrease in rate and extent of absorption was observed with north Indian diet and south Indian diet when compared with fasting group. Presence of both types of food causes decrease in mean values of C(max), AUC((0-t)), and AUC((0-alpha)) thus reducing the bioavailability of lamotrigine at significant level (P<0.05). INTERPRETATION AND CONCLUSION:Lamotrigine should be taken preferably in fasting condition, as presence of food (low fat, low calorie or high fat, high calorie) decreases the bioavailability to a significant extent.
Authors: Surulivelrajan Mallaysamy; Martin G Johnson; Padma G M Rao; Thiyagu Rajakannan; Lokesh Bathala; Karthik Arumugam; Johan G C van Hasselt; Devarakonda Ramakrishna Journal: Eur J Clin Pharmacol Date: 2012-06-02 Impact factor: 2.953