Makino Isao, Nakamura Kimihide, Sato Yoichi, Sato Yuzuru, Sezai Shuichi, Ikeda Yusei, Shinmura Wahei, Watahiki Hajime, Yamamoto Hideaki, Hioki Yayuki, Suzuki Masao, Kumada Takashi, Honda Takashi, Rikitoku Tomoo, Hisanaga Yasuhiro, Fukui Hiroshi, Yamao Junichi, Kawasaki Hironaka, Hosoda Akihide, Onji Morikazu, Matsui Hidetaka, Sata Michio, Torimura Takuji, Oho Kazuhiko, Maekawa Ryuichiro, Takagi Yoshiyuki, Shakado Satoshi, Nakayama Masafumi, Gondo Kazuhisa, Fukushima Hirofumi, Kusaba Taku, Tsubouchi Hirohito, Hayashi Katsuhiro, Hori Takeshi, Iida Yozo, Yutoku Kouki, Maetani Noboru, Kubo Yoshitsugu, Miyata Yoshifumi
Second Department of Internal Medicine, Asahikawa Medical College, Hokkaido, Japan.
Division of Gastroenterology, Kanto Medical Center NTT EC, Tokyo, Japan.
Curr Ther Res Clin Exp. 2006 Jan;67(1):1-20. doi: 10.1016/j.curtheres.2006.02.003.
Many Japanese patients with hepatic disorders confirmed on diagnostic imaging and coexisting upper gastrointestinal (GI) peptic lesions receive treatment with proton pump inhibitors. Some pharmacotherapies used to treat peptic ulcers have been associated with adverse drug reactions (ADRs), including elevated liver enzyme levels.
The aim of this study was to determine the tolerability and effectiveness of rabeprazole sodium in treating peptic lesions in patients with coexisting hepatic disorders.
This open-label, practice-based, postmarketing surveillance investigation was conducted at 15 centers across Japan. Male and female patients aged ≥18 years with peptic lesions confirmed on upper GI endoscopy and with underlying hepatic disease were enrolled. Patients were randomly assigned to receive rabeprazole 10 or 20 mg PO (tablet) QD after a meal for up to 8 weeks. Tolerability was assessed using monitoring of the incidence of ADRs determined by direct patient questioning, spontaneous reporting, and laboratory assessment. All patients who received at least 1 dose of study drug were included in the tolerability assessment. Effectiveness was assessed at baseline and study end using the rates of achievement of improvement on endoscopy, relief of subjective/objective symptoms (rates of improvement in epigastric pain and heartburn), and global improvement. The effectiveness analysis included all patients with complete data before and after treatment. Subanalyses were conducted to determine the effectiveness of drug by identification of the proportion of patients with coexisting hepatic disorders (cirrhosis, chronic hepatitis, and other hepatic diseases [eg, alcoholic hepatitis, fatty liver]) and by peptic lesion (gastric ulcer, duodenal ulcer, stomal ulcer, and reflux esophagitis) who achieved improvement.
A total of 114 patients were enrolled; 108 patients were included in the tolerability analysis (81 men, 27 women; mean age, 59.9 years; 10-mg dose, 90 patients; 20-mg dose, 18 patients) and 98 patients were included in the analysis of effectiveness. Twenty-one ADRs occurred in 11 (10.2%) patients. Serious ADRs occurred in 2 patients (elevated bilirubin level and hepatic encephalopathy, 1 patient each). Administration of rabeprazole was discontinued in 5 patients due to the occurrence of the following ADRs: constipation (1 patient); epigastric pain (1); dyslalia, disorientation, tremor, sleep disorder, and hepatic encephalopathy (1); diarrhea (1); and elevated alkaline phosphatase and y-glutamyl transpeptidase levels (1). On endoscopy, the proportion of patients achieving improvement with either dose was 30/33 (90.9%). The relief rates assessed using subjective symptoms were 47/55 (85.5%) and 47/56 (83.9%) for epigastric pain and heartburn, respectively. The proportion of patients achieving global improvement with either dose was 80/98 (81.6%) patients (49/62 [79.0%] for cirrhosis, 11/16 [68.8%] for chronic hepatitis, and 20/20 [100.0%] for other hepatic diseases [alcoholic hepatitis, fatty liver]).
In this study in Japanese patients with hepatic disorders, rabeprazole was well tolerated and appeared effective for the treatment of upper GI peptic lesions.
许多经诊断成像确诊患有肝脏疾病且并存上消化道（GI）消化性病变的日本患者接受质子泵抑制剂治疗。一些用于治疗消化性溃疡的药物疗法与药物不良反应（ADR）相关，包括肝酶水平升高。
本研究的目的是确定雷贝拉唑钠治疗并存肝脏疾病患者消化性病变的耐受性和有效性。
这项开放标签、基于实践的上市后监测调查在日本各地的15个中心进行。纳入年龄≥18岁、经上消化道内镜检查确诊患有消化性病变且患有基础肝脏疾病的男性和女性患者。患者被随机分配在餐后口服雷贝拉唑10或20mg（片剂），每日一次，疗程最长8周。通过直接询问患者、自发报告和实验室评估来监测ADR发生率，以此评估耐受性。所有接受至少1剂研究药物的患者均纳入耐受性评估。在基线和研究结束时，通过内镜检查改善的达成率、主观/客观症状的缓解情况（上腹部疼痛和烧心的改善率）以及整体改善情况来评估有效性。有效性分析纳入所有治疗前后有完整数据的患者。进行亚组分析，以确定并存肝脏疾病（肝硬化、慢性肝炎和其他肝脏疾病[如酒精性肝炎、脂肪肝]）患者以及消化性病变（胃溃疡、十二指肠溃疡、吻合口溃疡和反流性食管炎）患者中实现改善的比例，从而确定药物的有效性。
共纳入114例患者；108例患者纳入耐受性分析（男性81例，女性27例；平均年龄59.9岁；10mg剂量组90例患者，20mg剂量组18例患者），98例患者纳入有效性分析。11例（10.2%）患者发生21次ADR。2例患者发生严重ADR（胆红素水平升高和肝性脑病，各1例）。5例患者因发生以下ADR而停用雷贝拉唑：便秘（1例）；上腹部疼痛（1例）；构音障碍、定向障碍、震颤、睡眠障碍和肝性脑病（1例）；腹泻（1例）；碱性磷酸酶和γ-谷氨酰转肽酶水平升高（1例）。在内镜检查中，两种剂量下实现改善的患者比例为30/33（90.9%）。使用主观症状评估的上腹部疼痛和烧心的缓解率分别为47/55（85.5%）和47/56（83.9%）。两种剂量下实现整体改善的患者比例为80/98（81.6%）患者（肝硬化患者49/62[79.0%]，慢性肝炎患者11/16[68.8%]，其他肝脏疾病[酒精性肝炎、脂肪肝]患者20/20[100.0%]）。
在这项针对日本肝脏疾病患者的研究中，雷贝拉唑耐受性良好，似乎对上消化道消化性病变有效。
