INHIBITION OF GASTRIC ACID SECRETION BY INTRAVENOUS ANTOPRAZOLE

静脉注射安托拉唑抑制胃酸分泌

• 批准号: 6274557
• 负责人: DAVID C METZ
• 金额: $ 2.5万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-15 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6274557
• 关键词: antacids; clinical research; clinical trials; drug screening /evaluation; gastric acid; gastrointestinal disorder chemotherapy; human subject; human therapy evaluation; inhibitor /antagonist; intravenous administration; stomach disorder

Parenteral control of gastric acid hypersecretion in ZES patients is neccessary perioperatively or when oral medications cannot be taken for other reasons (e.g. during chemotherapy). IV histamine H2-receptor antagonists (H2RA) are able to control AO but very high doses of continuously infused agents are required. In the current study we evaluated the efficacy and safety of 15 min IV infusions of the proton pump inhibitor, PANTO (80-120 mg, q8h-q12h) in controlling AO for up to 7 days in 10 ZES patients (mean age 52.8 yrs [range 32-64], disease duration 6.9 yrs [range 1-16]). Effective control was defined as an AO <10 mEq/h (<5 mEq/h in patients with prior acid-reducing surgery). 4 patients were male, 3 had MEN-1 syndrome, 2 had prior acid-reducing surgery (both Whipple's operations), 1 had previously received chemotherapy and 5 (including the 2 with Whipple's operations) had undergone gastrinoma resections but none were cured. Prior to the study, AO was managed with oral PPIs in all patients (9 with omeprazole [20 mg QD to 60 mg BID] and one with lansoprazole [30 mg BID]). Mean (+/- SEM) prestudy basal acid output (BAO) in the absence of other PPIs for 7 days and H2RAs for 30 hrs was 37.8+6.9 mEq/h (range 15.2-84.5). Following an initial IV dose of 80 mg of PANTO, AO was controlled within the first hr in all patients. Mean AO 24 and 48 hours after the first IV PANTO dose was 3.6 +/- 1.1 and 2.6 +/- 2.8 mEq/h, respectively. A dose of 80 mg q12h was effective in 7/10 patients (70%) for up to seven days. 3 patients required upward dose titration. AO increased above the control value in the 9th hr after the first dose in 1 patient (a sporadic ZES male with a prior gastrinoma resection) and the dose was increased to 120 mg q12h with effective control thereafter. AO increased above the control value within 3 hrs in two patients (an MEN-1 syndrome male and a sporadic ZES female, neither with prior gastrinoma surgery). The dose was increased to 80 mg q8h with effective control in both patients within 24 hrs of dose escalation. At offset, AO remained controlled for 6 hours beyond the next expected dose in 8 patients. Breakthrough occured in the remaining 2 patients (BAO 47.9 and 48.3) after 3 and 5 hrs, respectively. No adverse events were noted. Thus, 160 mg of IV PANTO given in 2 divided doses controlled AO for up to 7 days in 70% of ZES patients. A higher daily divided dose of 240 mg IV controlled AO in all patients. IV PANTO provides significant advantages over existing methods for rapid and effective control of AO in ZES patients who cannot take oral agents.

塞米松患者胃酸高分泌的肠外控制 围手术期或不能口服药物的情况下 其他原因(如化疗期间)。静脉注射组胺H2受体 拮抗剂(H2RA)能够控制AO，但非常高剂量的 需要持续输注剂。在目前的研究中，我们 评价静脉注射15min质子的有效性和安全性 泵抑制剂泛图(80-120 mg，q8h-q12h)控制血管紧张素转换酶 10例癫痫患者，平均年龄52.8岁[范围32-]，疾病 持续时间6.9年[范围1-16])。有效的控制被定义为 AO&lt；10mEq/h(在既往减酸手术患者中为&lt；5mEq/h)。 4例为男性，3例为男性-1综合征，2例有既往减酸史 手术(两次惠普尔手术)，1人之前接受过 化疗和5例(包括2例惠普尔手术) 接受了胃泌素瘤切除，但无一治愈。在研究之前， 所有患者均接受口服PPI治疗(9例使用奥美拉唑[20 Mg qd至60 mg Bid]和兰索拉唑[30 mg Bid])。平均值(+/- 扫描电子显微镜)在没有其他PPI的情况下进行预研究基酸输出(BaO) 7d，30h的H_2RAS为37.8±6.9mEq/h(15.2~84.5)。 在最初静脉注射80毫克泛妥钠后，AO被控制在 所有患者的第一个小时数。第一次发作后24小时和48小时的平均声压 静脉注射泛素剂量分别为3.6±1.1和2.6±2.8mEq/h。一个 剂量为80 mg，q12h的有效率为7/10(70%)，最多为7次。 几天。3例患者需要向上剂量滴定。Ao增加到高于 1名患者在第一次服药后9小时内的控制值(a 曾接受过胃泌素瘤切除的男性)，剂量为 增加到120 mg，q12h，此后有效控制。AO增加 两名患者在3小时内超过控制值(一例MAN-1综合征 男性和零星的女性，均未做过胃泌素瘤手术)。 剂量增加到80 mg，q8h，两组均有效控制 患者在剂量升级后24小时内。在偏移时，AO保持不变 8例患者在超过下一个预期剂量后6小时内控制。 其余2例突破(BAO 47.9和48.3) 分别在3小时和5小时后。未发现任何不良反应。因此，160 静脉注射泛妥英钠毫克，分2个剂量控制，最多7天 在70%的ZES患者中。较高的每日分割剂量240毫克静脉注射 所有患者均控制在正常范围内。IV泛音提供了显著的优势 快速有效控制玉米体内急性呼吸窘迫综合征的现有方法 不能服用口服药物的患者。