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Beverage-induced enhanced bioavailability of carbamazepine and its consequent effect on antiepileptic activity and toxicity
Authors:Sanmoy Karmakar  Sreerupa Biswas  Rammohan Bera  Samiran Mondal  Amit Kundu  Md Asif Ali  Tuhinadri Sen
Affiliation:aDivision of Pharmacology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India; bSchool of Natural Product Studies, Jadavpur University, 188 Raja S.C. Mallick Road, Kolkata 700032, India; cAnimal Health Centre, Purulia, West Bengal, India
Abstract: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.
Keywords:bioavailability   black tea   carbamazepine   grapefruit juice   HPLC
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