奥普力农在肝脏手术中的I期临床试验。

Phase I clinical trial of olprinone in liver surgery.

作者信息

Fuji Hiroaki, Hatano Etsuro, Iguchi Kohta, Yamanaka Kenya, Yoh Tomoaki, Ikeno Yoshinobu, Seo Satoru, Taura Kojiro, Yasuchika Kentaro, Tanaka Shiro, Ishii Hisanari, Kobayashi Mariko, Ueno Kazuyuki, Uemoto Shinji

机构信息

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan.

出版信息

Surg Today. 2017 Aug;47(8):918-927. doi: 10.1007/s00595-016-1461-y. Epub 2016 Dec 27.

DOI:10.1007/s00595-016-1461-y

PMID:28028637

Abstract

PURPOSE

Post-hepatectomy liver failure is one of the most serious complications liver surgeons must overcome. We previously examined olprinone, a selective phosphodiesterase III inhibitor, and demonstrated its hepatoprotective effects in rats and pigs. We herein report the results of a phase I clinical trial of olprinone in liver surgery (UMIN000004975).

METHODS

Twenty-three patients who underwent hepatectomy between 2011 and 2015 were prospectively registered. In the first 6 cases, olprinone (0.1 μg/kg/min) was administered for 24 h from the start of surgery. In the remaining 17 cases, olprinone (0.05 μg/kg/min) was administered from the start of surgery until just before the transection of the liver parenchyma. The primary endpoint was safety, and the secondary endpoint was efficacy. For the evaluation of efficacy, the incidence of post-hepatectomy liver failure in 20 hepatocellular carcinoma patients was externally compared with 20 propensity score-matched patients.

RESULTS

No intraoperative side effects were observed, and the morbidity rates in the analyzed cohorts were acceptable. The rate of post-hepatectomy liver failure frequency tended to be lower in the olprinone group.

CONCLUSIONS

The safety of olprinone in liver surgery was confirmed. The efficacy of olprinone will be re-evaluated in clinical trials.

摘要

目的

肝切除术后肝衰竭是肝脏外科医生必须克服的最严重并发症之一。我们之前研究了选择性磷酸二酯酶III抑制剂奥普力农，并在大鼠和猪身上证明了其肝脏保护作用。我们在此报告奥普力农在肝脏手术中的I期临床试验结果（UMIN000004975）。

方法

前瞻性登记了2011年至2015年间接受肝切除术的23例患者。在前6例中，从手术开始给予奥普力农（0.1μg/kg/min）持续24小时。在其余17例中，从手术开始至肝实质离断前给予奥普力农（0.05μg/kg/min）。主要终点是安全性，次要终点是疗效。为评估疗效，将20例肝细胞癌患者肝切除术后肝衰竭的发生率与20例倾向评分匹配的患者进行外部比较。