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

Sanmoy Karmakar; Sreerupa Biswas; Rammohan Bera; Samiran Mondal; Amit Kundu; Md Asif Ali; Tuhinadri Sen

doi:10.1016/j.jfda.2014.07.012

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

J Food Drug Anal. 2015 Jun;23(2):327-334. doi: 10.1016/j.jfda.2014.07.012. Epub 2014 Dec 3.

Authors

Sanmoy Karmakar¹, Sreerupa Biswas², Rammohan Bera², Samiran Mondal³, Amit Kundu², Md Asif Ali², Tuhinadri Sen⁴

Affiliations

¹ Division of Pharmacology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India; School of Natural Product Studies, Jadavpur University, 188 Raja S.C. Mallick Road, Kolkata 700032, India. Electronic address: sanmoykarmakar@gmail.com.
² Division of Pharmacology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
³ Animal Health Centre, Purulia, West Bengal, India.
⁴ Division of Pharmacology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India; School of Natural Product Studies, Jadavpur University, 188 Raja S.C. Mallick Road, Kolkata 700032, 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 C_max as well as T_max 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: HPLC; bioavailability; black tea; carbamazepine; grapefruit juice.

Grants and funding

We would like to extend our sincere thanks to All India Council for Technical Education – Research Promotion Scheme (AICTE-RPS), the Government of India, University Grants Commission – Department of Special Assistance (UGC DSA), and University Grants Commission – Universities with Potential for Excellence Phase II (UGC UPE-II) for providing the financial support needed for this study.