Beverage-induced enhanced bioavailability of carbamazepine and its consequent effect on antiepileptic activity and toxicity

The present study was undertaken to investigate the food–drug interaction of carbamazepine (CBZ). Common fruit juices [grapefruit juice (GFJ), lime juice (LJ)], known to inhibit the enzyme cytochrome P450 3A4 (CYP3A4), and some widely consumed beverages [milk (M), black tea (BT)] were involved in this study in the presence of CBZ, as might happen during clinical therapy. The effects of the beverages on the pharmacokinetics and drug-induced toxicity of CBZ was observed after concomitant administration for a period of 28 days. Accordingly, the influence of altered bioavailability of CBZ on its antiepileptic activity was investigated. A significant shift in the Cmax as well as Tmax of CBZ was observed in the presence of LJ and GFJ. This increase in bioavailability significantly enhanced hepatotoxicity and delayed the onset of tremor and piloerection against pentylene tetrazole (PTZ)-induced seizure in experimental animals. However, increased toxicity of CBZ was found to be absent with BT. Thus, from our observation, LJ or GFJ in the presence of CBZ significantly increased the bioavailability of CBZ, which might lead to increased toxicity and antiepileptic activity of the drug.