フルテキストファイル
著者
Yang Jie Division of Pharmacology, School of Medicine, Tottori University Faculty of Medicine
Hasegawa Junichi National Hospital Organization Yonago Medical Center
Endo Yusuke Advanced Medicine, Innovation and Clinical Research Center, Tottori University Hospital 鳥取大学研究者総覧
Iitsuka Kazuhiko Division of Pharmacology, School of Medicine, Tottori University Faculty of Medicine
Yamamoto Miwa Department of Adult and Elderly Nursing, School of Health of Science, Tottori University Faculty of Medicine 鳥取大学研究者総覧 KAKEN研究者をさがす
Matsuda Akiko Faculty of Nursing, Nara Medical University
キーワード
absorption
drug interactions
herbal medicine
pharmacokinetics
rosuvastatin
抄録
Background Tanjin is an herbal medicine made from the root of salvia miltiorrhiza. It is predominantly given to arteriosclerotic patients as a supplement to ameliorate the clinical symptoms of cardiovascular diseases. In China, tanjin is used frequently in combination treatment for hypercholesterolemia. Thus, there is a high probability of combination of tanjin and statins in these arteriosclerotic patients. This study investigated the interaction between tanjin and rosuvastatin.

Methods We performed a randomized single-blind, two-period crossover clinical trial on six healthy male volunteers. Volunteers were administered rosuvastatin with placebo or a tanjin-containing drug randomly. The blood samples were collected before drug administration, and at 0.5, 1, 1.5, 2, 4, 8, and 12 hours after administration. Lymphocytes were isolated from blood samples before and 12 hours after drug administration to measure mRNA. As an animal experiment, an in situ intestinal injection with portal vein sampling model was used to examine the interaction between tanjin and rosuvastatin during the absorption phase. Rosuvastatin or rosuvastatin combined with tanjin solution was injected into the intestine. After injection, blood from the portal vein was collected and the concentration of rosuvastatin was measured by LC/MS/MS analysis. A portion of the intestine and liver from the rats was collected and stored at –80°C for mRNA measurement.

Results In the clinical trial, co-administration of tanjin decreased the maximum plasma concentration (Cmax) of rosuvastatin by 26.85% compared with rosuvastatin alone, and also decreased the area under the plasma concentration-time curve of rosuvastatin from 0 to 12 h (AUC0–12) by 19.43%. The relative expression of BCRP and OATP mRNA in human lymphocytes was increased by co-administration of tanjin. In the animal experiment, co-administration of tanjin extract reduced the concentration of rosuvastatin to 84.4, 64.4, and 50.0% at 15, 30, and 45 minutes, respectively. The tanjin-containing drug had a similar effect to tanjin extract. Furthermore, tanjin significantly reduced the absorption of rosuvastatin and the inhibitory effects lasted for at least 24 hours. Tanjin increased the relative expression of BCRP mRNA in the intestine, but it did not change the expression of OATP. Moreover, the concentration of rosuvastatin in the portal vein and systemic blood was reduced. In the liver, tanjin increased both BCRP and OATP mRNA expression, which was consistent with the results from human lymphocytes.

Conclusion The clinical trial and animal experiment revealed that tanjin can significantly reduce the absorption of rosuvastatin. This interaction occurred, at least, at the absorption phase in the small intestine due to the enhanced efflux transport. Thus, as tanjin and rosuvastatin were found to interact, their combination needs to be paid attention to.
出版者
Tottori University Medical Press
資料タイプ
学術雑誌論文
外部リンク
ISSN・ISBN
05135710
書誌ID
AA00892882
掲載誌名
Yonago Acta Medica
最新掲載誌名
Yonago Acta Medica
62
1
開始ページ
77
終了ページ
84
発行日
2019-03-28
出版者DOI
著者版フラグ
出版社版
著作権表記
注があるものを除き、この著作物は日本国著作権法により保護されています。 / This work is protected under Japanese Copyright Law unless otherwise noted.
掲載情報
Yonago Acta Medica. 2019, 62(1), 77-84
部局名
医学部・医学系研究科・医学部附属病院
言語
英語