Herbal medicine yin zhi huang induces CYP3A4-mediated sulfoxidation and CYP2C19-dependent hydroxylation of omeprazole.
OBJECTIVE
To explore the potential interactions between yin zhi huang (YZH) and omeprazole, a substrate of CYP3A4 and CYP2C19.


METHODS
Eighteen healthy volunteers, including 6 CYP2C19*1/*1, 6 CYP2C19*1/*2 or *3 and 6 CYP2C19*2/*2 were enrolled in a 2-phase, randomized, crossover clinical trial. In each phase, the volunteers received either placebo or 10 mL YZH oral liquid, 3 times daily for 14 d. Then all the patients took a 20 mg omeprazole capsule orally. Blood samples were collected up to 12 h after omeprazole administration. Plasma concentrations of omeprazole and its metabolites were quantified by HPLC with UV detection.


RESULTS
After 14 d of treatment of YZH, plasma omeprazole significantly decreased and those of omeprazole sulfone and 5-hydroxyomeprazole significantly increased. The ratios of the area under the plasma concentration-time curves from time 0 to infinity (AUC(0-infinity) of omeprazole to 5-hydroxyomprazole and those of omeprazole to omeprazole sulfone decreased by 64.80%+/-12.51% (P=0.001) and 63.31%+/-18.45% (P=0.004) in CYP2C19*1/*1, 57.98%+/-14.80% (P=0.002) and 54.87%+/-18.42% (P=0.003) in CYP2C19*1/*2 or *3, and 37.74%+/-16.07% (P=0.004) and 45.16%+/-15.54% (P=0.003) in CYP2C19*2/*2, respectively. The decrease of the AUC(0-infinity) ratio of omeprazole to 5-hydroxyomprazole in CYP2C19*1/*1 and CYP2C19*1/*2 or *3 was greater than those in CYP2C19*2/*2 (P=0.047 and P=0.009).


CONCLUSIONS
YZH induces both CYP3A4-catalyzed sulfoxidation and CYP2C19-dependent hydroxylation of omeprazole leading to decreases in plasma omeprazole concentrations.
Fan
Lan
L
Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Hu-nan 410078, China.
Wang
Guo
G
Wang
Lian-Sheng
LS
Chen
Yao
Y
Zhang
Wei
W
Huang
Yuan-Fei
YF
Huang
Rui-Xue
RX
Hu
Dong-Li
DL
Wang
Dan
D
Zhou
Hong-Hao
HH
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000097:blood; D000328:Adult; D000897:Anti-Ulcer Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D019540:Area Under Curve; D019306:Artemisia / Q000737:chemistry; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism*; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D005838:Genotype; D041743:Herb-Drug Interactions; D006801:Humans; D006900:Hydroxylation / Q000187:drug effects; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D010946:Plants, Medicinal / Q000737:chemistry; D012451:Safrole / Q000031:analogs & derivatives / Q000378:metabolism
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; C070600:yin zhi huang; C040450:omeprazole sulfone; C049963:5-hydroxymethylomeprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D009853:Omeprazole; D012451:Safrole; C005746:sulfoxide