Open AccessHerbal medicine Yin Zhi Huang induces CYP3A4‐mediated sulfoxidation and CYP2C19‐dependent hydroxylation of omeprazole 1
Author(s) -
FAN Lan,
WANG Guo,
WANG Liansheng,
CHEN Yao,
ZHANG Wei,
HUANG Yuanfei,
HUANG Ruixue,
HU Dongli,
WANG Dan,
ZHOU Honghao
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00617.x
Subject(s) - omeprazole , cyp2c19 , cyp3a4 , pharmacology , proton pump inhibitor , placebo , crossover study , medicine , chemistry , metabolism , cytochrome p450 , pathology , alternative medicine
Aim: 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‐∞) 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‐∞) 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). Conclusion: YZH induces both CYP3A4‐catalyzed sulfoxidation and CYP2C19‐dependent hydroxylation of omeprazole leading to decreases in plasma omeprazole concentrations.