Mai Ingrid, Bauer Steffen, Perloff Elke S, Johne Andreas, Uehleke Bernhard, Frank Bruno, Budde Klemens, Roots Ivar
Institute of Clinical Pharmacology, Departmetn of Naturopathy, Charité-University Medicine Berlin, Germany.
Clin Pharmacol Ther. 2004 Oct;76(4):330-40. doi: 10.1016/j.clpt.2004.07.004.
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.
贯叶连翘（SJW）与其他药物合用时，许多药物的生物利用度降低，而金丝桃素（HYF）被认为是其潜在原因。本研究比较了两种HYF含量高低不同的SJW制剂对环孢素（国际非专利药品名称，环孢菌素）（CSA）药代动力学的影响。
在一项交叉研究中，10名肾移植患者被随机分为两组，除常规服用CSA外，分别接受低浓度或高浓度HYF的SJW提取物（900mg/d），共14天。经过27天的洗脱期后，患者交叉接受另一种SJW治疗，为期14天。通过免疫测定法测量CSA的血药浓度。
研究表明，两种SJW制剂对CSA药代动力学的影响存在显著差异（一个给药间隔内血浆浓度-时间曲线下面积[AUC0-12]，P<.0001，方差分析）。与低HYF含量的SJW合用时，高HYF含量的SJW使AUC0-12值（单克隆）降低了45%（95%置信区间[CI]，-37%至-54%；P<.05，Student-Newman-Keuls检验）。与低HYF含量的SJW相比，高HYF含量的SJW与CSA合用时2周后，CSA（单克隆）的剂量校正AUC0-12与基线相比显著降低了52%（95%CI，-46%至-56%；P<.05）。血浆峰浓度和一个给药间隔结束时的药物浓度值受到的影响程度相似，分别降低了43%（95%CI，-36%至-48%）和55%（95%CI，-48%至-60%）。此外，在高HYF含量的SJW治疗期间，每日CSA剂量需要增加65%（95%CI，53%至85%；P<.05）。相比之下，低HYF含量的SJW与CSA合用对CSA药代动力学无显著影响，与基线相比也无需调整CSA剂量。
SJW提取物中的HYF含量显著影响CSA与SJW之间药代动力学相互作用的程度。
