Liu Wei Di Huang Wan, a well-known traditional Chinese medicine, induces CYP1A2 while suppressing CYP2A6 and N-acetyltransferase 2 activities in man

Ethnopharmacological relevance: Liu Wei Di Huang Wan (LDW), a well-known traditional Chinese medicine, is frequently combined with other prescription or non-prescription drugs in China. Aim of the study: This study was designed to investigate the effects of LDW on the activities of CYP1A2, CYP2A6, N-acetyltransferase 2 (NAT2) and xanthine oxidase (XO) in healthy subjects, using caffeine as a probe drug. Materials and methods: Twelve unrelated healthy males were enrolled in a single-blind, randomized, placebo-controlled, two-phase crossover study. Placebo or LDW (12 pills, 0.2 g/pill, twice daily) was given to each participant for 14 continuous days with a wash-out period of 2 weeks. A dose of 100 mg caffeine was given afterwards to test the activities of drug-metabolizing enzymes of interest. Results: Compared to placebo, LDW significantly induced the CYP1A2 activity, as determined by an increase in the ratio of (AFMU + 1U + 1X)/17U and the formation of 17X and 1X after taking caffeine. Interestingly, LDW significantly decreased the ratio of 17U/(17U + 17X + 1X + 1U + AFMU) and the formation of 17U (CYP2A6-mediated) (by 39.2%; 95%CI: 23.1-55.3%; P=0.026), and decreased the ratio of AFMU/(AFMU+1U+1X) and the formation of AFMU (NAT2-catalized) (by 26.2%; 95%CI: 9.2-61.6%; P=0.038), suggesting a marked inhibition of CYP2A6 and NAT2, respectively. Conclusions: LDW can induce CYP1A2 and suppress CYP2A6 and NAT2 activities, and affect caffeine metabolism in vivo. (C) 2010 Elsevier Ireland Ltd. All rights reserved.