Effect of a traditional Chinese medicine Liu Wei Di Huang Wan on the activities of CYP2C19, CYP2D6 and CYP3A4 in healthy volunteers.
Liu Wei Di Huang Wan (LDW), a well-known traditional Chinese medicine, is widely used for the treatment of various diseases in China. This study was designed to investigate the potential herb-drug interactions of LDW in healthy volunteers and attempted to ascertain whether the interaction might be affected by genotypes.        We assessed the effect of LDW on the activities of CYP2C19, CYP2D6 and CYP3A4 in 12 Chinese healthy subjects in a single-center, controlled, non-blinded, two-way crossover clinical trial. The subject pool consisted of six extensive metabolizers with CYP2C19*1/*1 and six poor metabolizers with CYP2C19*2/*2. Placebo or 4.8 g 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 after an oral administration of 30 mg omeprazole, 30 mg dextromethorphan hydrobromide and 7.5 mg midazolam. The activities of CYP2C19, CYP2D6 and CYP3A4 were ascertained by their respective plasma or urinary metabolic ratios on day 14 post-treatment.        There is no difference in the activities of the three tested enzymes before or after a 14-day administration of LDW. LDW had no effect on the pharmacokinetic parameters of the substrates and their metabolites.        A 14-day administration of LDW did not affect the activities of CYP2C19, CYP2D6 and CYP3A4. LDW is unlikely to cause pharmacokinetic interaction when it is combined with other medications predominantly metabolized by these enzymes.
Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.
Y
Y
Chen
D-S
DS
Ouyang
Z
Z
Kang
G-P
GP
Yang
Z-R
ZR
Tan
G
G
Zhou
J
J
Yan
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000097:blood* / Q000235:genetics; D002681:China; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000097:blood* / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000097:blood* / Q000235:genetics; D003915:Dextromethorphan / Q000008:administration & dosage / Q000493:pharmacokinetics; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005838:Genotype; D041743:Herb-Drug Interactions; D006801:Humans; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000493:pharmacokinetics; D009853:Omeprazole / Q000008:administration & dosage / Q000493:pharmacokinetics; D010919:Placebos
D004365:Drugs, Chinese Herbal; D010919:Placebos; C476907:liu-wei-di-huang wan; D003915:Dextromethorphan; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D009853:Omeprazole; D008874:Midazolam