Capsaicin, a major ingredient of hot pepper, has been known to affect on activities of several CYP isoenzymes. To evaluate the effect of hot pepper on activities of CYP2A6 and other CYPs, 7 healthy subjects predetermined to have no CYP2A6, 2C19 and 2D6 genetic variation reported previously were enrolled in randomized crossover study. In the restriction period, food containing hot pepper was completely restricted for 7 days. In other period, meal containing 5g of hot pepper was served three times a day for 7 days. On each 6th day, cocktail study including PO caffeine, omeprazole, and dextromethophan, and IV midazolam was conducted. On 7th day, nicotine (2mg) gum was chewed for 30 min. Blood and urine were serially collected for 12 hrs after dosing. Concentrations of probes and their metabolites in plasma and urine were measured using LC/MS/MS and HPLC. The AUC12hr ratio of cotinine to nicotine was higher in hot pepper rich diet than in the restriction period. The t1/2of nicotine was shortened (8.7±6.3hr vs 3.7±1.8hr, p<0.05) and total clearance was increased significantly (1.0±0.5 vs 1.6±0.6L/kg/hr, p<0.05) after hot pepper rich diet. The metabolic ratio of other CYP isoforms was not significantly changed after hot pepper rich. Diet containing high content of hot pepper seems likely to increase CYP2A6 activity, but not other CYPs. Higher CYP2A6 activity in Korean may be contributed by high intake of hot pepper rich foods. This might imply that high smoking rates in Korean population is related with intake of hot pepper. Clinical Pharmacology & Therapeutics (2005) 77, P85–P85; doi:
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