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  • Title: Hyperforin content determines the magnitude of the St John's wort-cyclosporine drug interaction.
    Author: Mai I, Bauer S, Perloff ES, Johne A, Uehleke B, Frank B, Budde K, Roots I.
    Journal: Clin Pharmacol Ther; 2004 Oct; 76(4):330-40. PubMed ID: 15470332.
    Abstract:
    OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: HYF content of SJW extracts significantly affects the extent of the pharmacokinetic interaction between CSA and SJW.
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