Jackson Akil, D'Avolio Antonio, Moyle Graeme, Bonora Stefano, Di Perri Giovanni, Else Laura, Simiele Marco, Singh Gurmit Jagjit, Back David, Boffito Marta
St Stephen's Centre, Chelsea and Westminster Hospital, London, UK.
Department of Infectious Diseases, University of Turin, Turin, Italy.
J Antimicrob Chemother. 2014 Jul;69(7):1911-5. doi: 10.1093/jac/dku060. Epub 2014 Mar 6.
St John's wort (SJW; Hypericum perforatum) induces CYP3A4 that is involved in the metabolism of the hepatitis C virus (HCV) protease inhibitor boceprevir. Reduced boceprevir exposure and efficacy would contribute to therapeutic failure and increase the risk for resistance development. Boceprevir is co-administered with interferon/ribavirin, and depression has been described frequently in patients undergoing HCV treatment. Patients may purchase over-the-counter herbals to manage depression, and knowing the interaction between SJW and boceprevir is desirable.
This Phase I, open-label, three-period, cross-over pharmacokinetic study enrolled healthy males and females who, following consent and screening procedures, were randomized to receive SJW on days 1-14, SJW plus boceprevir (SJW on days 22-35 and together on days 31-35) and boceprevir on days 52-56, separated by 7 day washout periods, or the same treatment in the opposite order. Pharmacokinetic sampling was performed at the end of each phase.
Seventeen (11 female) subjects completed the study and no serious adverse events were reported. Geometric mean ratios (GMRs) and 90% CIs for boceprevir (with SJW versus alone) AUC(0-8), C(max) and C8 were 0.91 (0.87-0.96), 0.94 (0.82-1.07) and 1.00 (0.79-1.27), respectively. GMRs and 90% CIs for hypericin, the active component of SJW, (with boceprevir versus alone) AUC(0-8), C(max) and C(8) were 1.23 (1.10-1.38), 1.32 (1.16-1.52) and 1.37 (1.19-1.58), respectively.
SJW did not have a clinically significant effect on boceprevir plasma concentrations (or those of its metabolite), suggesting that SJW and boceprevir can be safely co-administered.
圣约翰草（SJW；贯叶连翘）可诱导细胞色素P450 3A4（CYP3A4），而该酶参与丙型肝炎病毒（HCV）蛋白酶抑制剂博赛匹韦的代谢。博赛匹韦的暴露量降低及疗效下降会导致治疗失败，并增加耐药性产生的风险。博赛匹韦与干扰素/利巴韦林联合使用，且接受HCV治疗的患者中经常出现抑郁症状。患者可能会购买非处方草药来治疗抑郁症，因此了解圣约翰草与博赛匹韦之间的相互作用很有必要。
这项I期开放标签、三阶段、交叉的药代动力学研究纳入了健康男性和女性，在获得同意并完成筛查程序后，将其随机分为三组，分别在第1 - 14天接受圣约翰草治疗，在第22 - 35天接受圣约翰草加博赛匹韦治疗（第31 - 35天两者同时使用），在第52 - 56天接受博赛匹韦治疗，每组治疗之间间隔7天的洗脱期，或采用相反顺序进行相同治疗。在每个阶段结束时进行药代动力学采样。
17名（11名女性）受试者完成了研究，未报告严重不良事件。博赛匹韦（联用圣约翰草与单用相比）的几何平均比值（GMRs）及90%置信区间（CIs），其药时曲线下面积（AUC(0 - 8)）、血药浓度峰值（C(max)）和给药后8小时血药浓度（C8）分别为0.91（0.87 - 0.96）、0.94（0.82 - 1.07）和1.00（0.79 - 1.27）。圣约翰草的活性成分金丝桃素（联用博赛匹韦与单用相比）的GMRs及90% CIs，其AUC(0 - 8)、C(max)和C(8)分别为1.23（1.10 - 1.38）、1.32（1.16 - 1.52）和1.37（1.19 - 1.58）。
圣约翰草对博赛匹韦的血浆浓度（或其代谢物的血浆浓度）没有临床显著影响，这表明圣约翰草和博赛匹韦可以安全地联合使用。
