Influence of caffeine on pharmacokinetic profile of sodium valproate and carbamazepine in normal human volunteers.

The present study evaluates effect of pharmacokinetic interaction between caffeine (300 mg) in three divided doses with sodium valproate (400 mg) and carbamazepine (200 mg) given as single doses, in normal human volunteers, using a open cross over design. Both the serum concentration of sodium valproate and pharmacokinetic parameters remained unaltered, as against significant reduction in plasma concentration and area under the concentration curve of carbamazepine following the coadministration of caffeine. Also, the plasma t 1/2 (of carbamazepine was prolonged by two folds and bioavailability reduced by about 32% in presence of caffeine. The results are of clinical significance as xanthine consumption may have to be restricted in patients on carbamazepine therapy and this aspect may need further investigation.