Hyperforin content determines the magnitude of the St John's wort-cyclosporine drug interaction

Hyperforin (HYF) has been discussed as a potential cause of the reduction in the bioavailability of numerous drugs seen with St John's wort (SJW) comedication. This study compared the effects of 2 SJW preparations with high and low HYF content on the pharmacokinetics of cyclosporine (INN, ciclosporin) (CSA).

In a crossover study, 10 renal transplant patients were randomized into 2 groups and received SJW extract (900 mg/d) containing low or high concentrations of HYF for 14 days in addition to their regular regimen of CSA. After a 27-day washout phase, patients were crossed over to the other SJW treatment for 14 days. Blood concentrations of CSA were measured by immunoassay.

The study showed a significant difference between the effects of the 2 SJW preparations on CSA pharmacokinetics (area under the plasma concentration-time curve within one dosing interval [AUC 0-12 ], P < .0001, ANOVA). AUC 0-12 values (monoclonal) with high-HYF SJW comedication were 45% lower (95% confidence interval [CI], -37% to -54%; P < .05, Student-Newman-Keuls test) than for low-HYF SJW. The dose-corrected AUC 0-12 for CSA (monoclonal) decreased significantly compared with baseline by 52% (95% CI, -46% to -56%; P < .05) after 2 weeks of comedication with high-HYF SJW. Values of peak concentration in plasma and drug concentration at the end of one dosing interval were affected to a similar extent, with reductions by 43% (95% CI, -36% to -48%) and 55% (95% CI, -48% to -60%), respectively. In addition, a 65% (95% CI, 53% to 85%; P < .05) increase in daily CSA doses was required during high-HYF SJW treatment. In contrast, coadministration of low-HYF SJW did not significantly affect CSA pharmacokinetics and did not require CSA dose adjustments compared with baseline.

HYF content of SJW extracts significantly affects the extent of the pharmacokinetic interaction between CSA and SJW.