著者

齊藤 将之 前田 徹 市原 利彦 岩尾 岳洋 鈴木 匡

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.140, no.10, pp.1269-1274, 2020-10-01 (Released:2020-10-01)

参考文献数

19

被引用文献数

1

---

We previously reported that tolvaptan may influence warfarin pharmacodynamics in vivo; however, the mechanism responsible for this influence was not clear. In this study, we investigated the drug-drug interactions between warfarin and tolvaptan by measuring warfarin blood concentrations in 18 patients who received warfarin therapy and in 24 who received warfarin+tolvaptan therapy. The free warfarin concentrations significantly increased in patients who were also receiving oral tolvaptan (p=0.04). In vitro albumin-binding experiments showed that the free warfarin concentrations significantly increased with the addition of tolvaptan, in a dose-dependent manner, through albumin-binding substitution (approximately 2.5 times). Both clinical and in vitro data showed that tolvaptan increased the unbound warfarin serum concentration. The prothrombin time-international normalized ratio (PT-INR) tended to increase within 2 weeks when tolvaptan was added at clinically used doses (p=0.14). Special attention is warranted in cases with a serum tolvaptan concentration of ≥125 ng/mL (≥7.5 mg/d) for at least 2 weeks following oral tolvaptan administration.

著者

中村 敏明 岩尾 岳洋 東 高士 谷 大輔 矢野 良一 政田 幹夫

出版者

一般社団法人日本医療薬学会

雑誌

医療薬学 (ISSN:1346342X)

巻号頁・発行日

vol.37, no.9, pp.551-558, 2011 (Released:2012-09-10)

参考文献数

13

---

Paclitaxel injection [NK] (PTX [NK]) is a generic of Taxol® Injection (Taxol) but no non-clinical study comparing the safety of the 2 drugs has been conducted because the active ingredient is the same.We compared the safety of PTX [NK] and Taxol in rats to see if there were any differences. PTX [NK] and Taxol were intravenously administered to CD (SD) male rats at doses of 2.0 and 4.0 mg/kg/day for 9 days. There were very slight differences in toxicological findings regarding such items as clinical observations, food consumption, gross necropsy, organ weight and histopathology. These differences, however, were generally observed after administration of a cytocidal anticancer drug. Therefore, such differences were not thought to be toxicologically significant and we concluded that the safety of PTX [NK] was no different from that of Taxol in rats.