Department of Neuropsychiatry, Bioregulatory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
J Clin Pharm Ther. 2011 Dec;36(6):711-5. doi: 10.1111/j.1365-2710.2010.01223.x. Epub 2010 Nov 8.
St John's wort (SJW, Hypericum perforatum) is one of the most commonly used herbal antidepressants for treatment of mild to moderate depression. SJW enhances CYP3A4 activity and alters the pharmacokinetics of CYP3A4 substrates. This study investigated the effect of SJW on the pharmacokinetics of zolpidem in healthy subjects.
A controlled, open-label, non-randomized, fixed-dose schedule design was used. Fourteen healthy male subjects received a single 10 mg oral dose of zolpidem followed by SJW administration (300 mg orally, three times a day) for 14 days; the last dose of SJW was coadministered with a single dose of zolpidem. Blood samples were obtained over a 24-h period after zolpidem administration. Pharmacokinetic data for zolpidem alone and in combination with SJW were analysed by high-performance liquid chromatography.
After repeated administration of SJW, the mean values of AUC and C(max) for zolpidem significantly decreased (380.3 ± 181.4 vs. 265.4 ± 134.2 ng h/mL, P = 0.001; 83.1 ± 30.1 vs. 55.1 ± 24.8 ng/mL, P = 0.000 respectively) and the mean value of CL/F for zolpidem significantly increased (38.4 ± 31.5 vs. 56.9 ± 57.2 mL/min, P = 0.040). However, in three subjects, the AUC showed a small increase after SJW treatment.
The effect of SJW on the pharmacokinetics of zolpidem has not previously been reported. Repeated administration of SJW decreases the plasma concentration of zolpidem, probably by enhancing CYP3A4 activity. Given the wide inter-subject variability observed, for personalized medicine, advice on the use of the combination should be individualized, based on the circumstances of the patient.
贯叶金丝桃（SJW，贯叶连翘）是最常用于治疗轻度至中度抑郁症的草药抗抑郁药之一。SJW 增强 CYP3A4 的活性并改变 CYP3A4 底物的药代动力学。本研究调查了 SJW 对健康受试者中佐匹克隆药代动力学的影响。
采用对照、开放标签、非随机、固定剂量方案设计。14 名健康男性受试者单次口服 10mg 佐匹克隆后，给予 SJW 治疗（300mg 口服，每日 3 次）14 天；SJW 的最后一剂与单剂量佐匹克隆同时给予。佐匹克隆给药后 24 小时内采集血样。单独和联合使用 SJW 时的佐匹克隆药代动力学数据通过高效液相色谱法进行分析。
重复给予 SJW 后，佐匹克隆的 AUC 和 Cmax 平均值显著降低（380.3 ± 181.4 与 265.4 ± 134.2ng h/mL，P=0.001；83.1 ± 30.1 与 55.1 ± 24.8ng/mL，P=0.000），佐匹克隆的 CL/F 平均值显著增加（38.4 ± 31.5 与 56.9 ± 57.2mL/min，P=0.040）。然而，在 3 名受试者中，SJW 治疗后 AUC 略有增加。
SJW 对佐匹克隆药代动力学的影响以前没有报道过。重复给予 SJW 可降低佐匹克隆的血浆浓度，可能是通过增强 CYP3A4 的活性。鉴于观察到的个体间变异性很大，对于个体化医学，应根据患者的具体情况，对联合用药的使用提出个体化建议。
