圣约翰草对甲磺酸伊马替尼药代动力学及蛋白结合率的影响。

The influence of St. John's wort on the pharmacokinetics and protein binding of imatinib mesylate.

作者信息

Smith Patrick, Bullock Julie M, Booker Brent M, Haas Curtis E, Berenson Charles S, Jusko William J

机构信息

School of Pharmacy and Pharmaceutical Sciences, University of Buffalo, Buffalo, New York, USA.

出版信息

Pharmacotherapy. 2004 Nov;24(11):1508-14. doi: 10.1592/phco.24.16.1508.50958.

DOI:10.1592/phco.24.16.1508.50958

PMID:15537555

Abstract

STUDY OBJECTIVE

To determine the effect of St. John's wort on the pharmacokinetics of imatinib mesylate.

DESIGN

Open-label, complete crossover, fixed-sequence, pharmacokinetic study.

SETTING

Clinical research center.

SUBJECTS

Ten healthy adult volunteers.

INTERVENTION

Single 400-mg oral doses of imatinib were administered before and after 2 weeks of treatment with St. John's wort 300 mg 3 times/day.

MEASUREMENTS AND MAIN RESULTS

The pharmacokinetics of imatinib were significantly altered by St. John's wort, with reductions of 32% in the median area under the concentration-time curve from time zero to infinity (p=0.0001), 29% in maximum observed concentration (p=0.005), and 21% in half-life (p=0.0001). Protein binding ranged from 97.7-90.3% (mean 94.9%), was concentration independent, and was not altered by St. John's wort. Therapeutic outcomes of imatinib have been shown to correlate with both dose and drug concentrations.

CONCLUSION

Coadministration of imatinib with St. John's wort may compromise imatinib's clinical efficacy.

摘要

研究目的

确定圣约翰草对甲磺酸伊马替尼药代动力学的影响。

设计

开放标签、完全交叉、固定顺序的药代动力学研究。

地点

临床研究中心。

受试者

10名健康成年志愿者。

干预措施

在每天3次服用300毫克圣约翰草治疗2周前后，分别单次口服400毫克伊马替尼。

测量指标及主要结果

圣约翰草显著改变了伊马替尼的药代动力学，从零时间到无穷大的浓度-时间曲线下面积中位数降低了32%（p = 0.0001），最大观察浓度降低了29%（p = 0.005），半衰期降低了21%（p = 0.0001）。蛋白结合率在97.7%至90.3%之间（平均94.9%），与浓度无关，且未被圣约翰草改变。伊马替尼的治疗效果已显示与剂量和药物浓度相关。