St John's wort induces both cytochrome P450 3A4–catalyzed sulfoxidation and 2C19–dependent hydroxylation of omeprazole

• DOI: 10.1016/j.clpt.2003.09.014
• Publication Date: 2004-03-06T10:39:24Z
• Authors: Lian‐Sheng Wang; Gan Zhou; Bing Zhu; Jun Wu; Jian‐Gang Wang; A. M. Abd El‐Aty; Tong Li; Jie Liu; Tian‐Lun Yang; Dan Wang; Xiang‐Yang Zhong; Hong‐Hao Zhou
• Keywords: Hydroxylation

Objective St John's wort, an extract of the medicinal plant Hypericum perforatum , is widely used as herbal antidepressant. Although ability wort to induce cytochrome P450 (CYP) 3A4–mediated reaction has been well established, effect on CYP2C19 still not determined. Thus objective this study was determine impact pharmacokinetic profiles omeprazole and its metabolites. Methods Twelve healthy adult men (6 CYP2C19*1 / 4 CYP2C19*2 2 CYP2C19*3 ) were enrolled in a 2‐phase randomized crossover design. In each phase volunteers received placebo or 300‐mg tablet 3 times daily for 14 days. Then all subjects took 20‐mg capsule orally. Blood samples collected up 12 hours after administration. Omeprazole metabolites quantified by use HPLC with ultraviolet detection. Results exhibit genotype–dependent profiles. After 14‐day treatment substantial decreases plasma concentrations observed. The peak concentration (C max significantly decreased 37.5% ± 13.3% ( P = .001) *3 49.6% 20.7% .017) ; area under concentration‐time curve extrapolated infinity [AUC(0‐∞)] 37.9% 21.3% .014) 43.9% 23.7% .011) mutant wild genotypes, respectively. Moreover, C AUC(0‐∞) sulfone increased 160.3% 45.5% 136.6% 84.6% .014), 155.5% 58.8% .001), 158.7% 101.4% 5‐hydroxyomeprazole 38.1% 30.5% .028) 37.2% 26% .005) wild‐type subjects, whereas it did produce any significant alterations corresponding parameters variant genotypes. Conclusion induces both CYP3A4‐catalyzed sulfoxidation CYP2C19‐dependent hydroxylation enormously omeprazole. Clinically relevant interactions other drugs may occur must be taken into account when being taken. Clinical Pharmacology & Therapeutics (2004) 75 191–197; doi: 10.1016/j.clpt.2003.09.014