Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy.
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.


CONCLUSIONS
Grapefruit juice increases the bioavailability of carbamazepine by inhibiting CYP3A4 enzymes in gut wall and in the liver.
Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
S K
SK
Garg
N
N
Kumar
V K
VK
Bhargava
S K
SK
Prabhakar
D000328:Adult; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001628:Beverages; D002220:Carbamazepine / Q000493:pharmacokinetics*; D002957:Citrus / Q000378:metabolism*; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014867:Water / Q000378:metabolism
D000927:Anticonvulsants; D014867:Water; D002220:Carbamazepine