Effect of Honey on CYP3A4 Enzyme and P-Glycoprotein Activity in Healthy Human Volunteers Abstract

The activity of cytochrome p450 isozyme 3A4 (CYP3A4) enzyme and P-glycoprotein (P-gp) is modulated by grapefruit juice and herbal drugs. CYP3A4 is the major phase I drug metabolizing enzyme and P-gp is an ATP-dependent drug efflux pump that regulates the intestinal absorption of orally administered drugs. Honey is commonly consumed as a dietary supplement. However, its influence on human CYP3A4 and P-gp activity is not yet well documented. Therefore, we investigated the influence of a 10-day honey administration on CYP3A4 and P-gp activity in healthy volunteers using carbamazepine and digoxin as their probe drugs respectively. A within-group pharmacokinetic study was done in 12 healthy volunteers. They were administered single oral dose of carbamazepine (200 mg) and digoxin (0.5 mg) before and after 10 days of honey (10 ml twice daily) intake. Blood samples (5ml) were collected at 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2, 4, 8, 12, 24, 48 and 72 h after drug administration. Concentration of carbamazepine and digoxin in plasma was measured by HPLC and RIA method respectively. Ten days of honey administration did not significantly alter the C max, Tmax and AUC (0-t) of carbamazepine (probe drug for CYP3A4) and digoxin (probe drug for P-gp). Our results suggest that honey may not significantly modulate the CYP3A4 enzyme and P-glycoprotein activity. The coadministration of honey with drugs may not result in significant drug interactions.