Objective: To examine the effect of grapefruit juice on the bioavailability of carbamazepine in patients with epilepsy.
Methods: This was a randomized crossover study consisting of 2 phases. Ten patients with epilepsy who had received therapy with 200 mg carbamazepine 3 times a day for the previous 3 to 4 weeks participated. They were given either grapefruit juice or 300 mL water at 8 am along with 200 mg carbamazepine. Each treatment was separated by 2 days; subjects continued to receive carbamazepine therapy during the 2-day period. On both occasions, blood samples were collected at different time intervals between 0 to 8 hours. Carbamazepine levels were estimated by reversed-phase HPLC technique.
Results: Compared with water, grapefruit significantly increased the steady peak concentration (6.55 versus 9.20 microgram/mL), trough concentration (4.51 versus 6.28 microgram/mL), and area under the plasma concentration-time curve (43.99 versus 61.95 micrograms.h/mL) of carbamazepine. No significant effect was found in the time to reach peak plasma concentration.
Conclusion: Grapefruit juice increases the bioavailability of carbamazepine by inhibiting CYP3A4 enzymes in gut wall and in the liver.