Liu wei di huang wan, a well-known traditional Chinese medicine, induces CYP1A2 while suppressing CYP2A6 and N-acetyltransferase 2 activities in man.
BACKGROUND
Liu wei di huang wan (LDW), a well-known traditional Chinese medicine, is frequently combined with other prescription or non-prescription drugs in China.


OBJECTIVE
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.


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-catalyzed) (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.
Chen
Yao
Y
Institute of Clinical Pharmacology, Central South University, 110 Xiang-Ya Road, Changsha, Hunan 410078, China.
Kang
Zhen
Z
Yan
Jin
J
Yang
Guo-Ping
GP
Tan
Zhi-Rong
ZR
Zhou
Gan
G
Ouyang
Dong-Sheng
DS
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors*; D002110:Caffeine / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D002681:China; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D065637:Cytochrome P-450 CYP2A6; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004790:Enzyme Induction; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D055815:Young Adult
D004365:Drugs, Chinese Herbal; C476907:liu-wei-di-huang wan; D002110:Caffeine; D001189:Aryl Hydrocarbon Hydroxylases; C504573:CYP1A2 protein, human; C585710:CYP2A6 protein, human; D019388:Cytochrome P-450 CYP1A2; D065637:Cytochrome P-450 CYP2A6; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human