Induction of CYP3A by St. Johns Wort (SJW) depends on hyperforin (HYF) dose

Abstract

Background Induction of CYP3A by SJW with high HYF content is known. SJW products vary in the amount of main constituents. The aim of the study was to evaluate the influence of SJW preparations with low and high HYF content on CYP3A function. Methods A one-sequence crossover study was performed in 42 male, healthy volunteers, who were randomized into 6 SJW groups. Midazolam (MDZ) plasma concentration profiles were characterized after a single oral dose of 7.5 mg MDZ on the day before and on the 14th day of SJW medication. Results Effect of SJW on % change in MDZ AUC 0–12h compared to baseline, mean and 95% confidence interval (CI): (see Table) Decrease in MDZ AUC was correlated with HYF content (r= −0.78, p<0.01). Conclusion Induction of CYP3A varies between SJW products. SJW products with low HYF content induce CYP3A significantly less than high HYF SJW products. The degree of induction depends on HYF dose. Clinical Pharmacology & Therapeutics (2005) 77, P36–P36; doi: 10.1016/j.clpt.2004.12.031 SJW dose/d (HYF content mg/d) Mean % change 95 %-CI 900mg extract LI 160 (41.25) −79.4 −88.6; −70.1 2.7g plant (0.13) −21.1 −33.9; −8.3 2.7g plant (12.06) −47.9 −59.7; −36.2 1.8g plant (8.04) −37.0 −58.2; −15.8 1.2g plant (5.36) −31.3 −45.3; −17.3 0.6g plant (2.68) −20.4 −40.0; −0.8