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: 6113323
• 负责人: DAVID C METZ
• 金额: $ 2.51万
• 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: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6113323
• 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.

在围手术期或由于其他原因不能服用口服药物时(如化疗期间)，对EES患者胃酸高分泌进行肠外控制是必要的。组胺H_2受体拮抗剂(H_2RA)能够控制AO，但需要非常高剂量的持续输注剂。在本研究中，我们评价了10例患者(平均年龄52.8岁[32-]，病程6.9年[1-16])静脉滴注质子泵抑制剂泛图(80-120 mg，q8h-q12h)15分钟控制AO的有效性和安全性。有效控制被定义为10mEq/h(在既往减酸手术患者中为5mEq/h)。4例男性，3例男性-1综合征，2例既往减酸手术(均为惠普尔手术)，1例曾接受化疗，5例(包括2例惠普尔手术)曾接受胃泌素瘤切除，但均未治愈。在研究之前，所有患者(9名使用奥美拉唑[每天20毫克至60毫克，每日2次]，1名使用兰索拉唑[30毫克，每日2次])接受口服PPI治疗。在没有其他PPI 7天和H2RAS 30小时的研究前平均(+/-SEM)基础酸产量(BAO)为37.8±6.9mEq/h(范围15.2-84.5)。在最初静脉注射80毫克泛妥钠后，所有患者的AO都在第一小时内得到控制。首次静脉注射潘托品后24小时和48小时的平均动脉压分别为3.6±1.1和2.6±2.8mEq/h。剂量为80 mg，q12h的有效率为7/10(70%)，持续时间长达7天。3例患者需要向上剂量滴定。1例(1例零星男性，有胃泌素瘤切除史)首次用药后第9小时血氧高于对照组，剂量增至120 mg，q12h后有效控制。两名患者(1名男性-1综合征男性和1名散发性女性，均未做过胃泌素瘤手术)在3小时内超过控制值。剂量增加到80 mg，q8h，两名患者在剂量增加后24小时内均得到有效控制。在偏移量时，8名患者在下一个预期剂量之后6小时内保持控制状态。其余2例(BAO47.9和48.3)分别在3h和5h后发生突破。未发现任何不良反应。因此，在70%的ZES患者中，分两次给予160 mg静脉注射泛影葡胺可控制AO，持续时间长达7天。在所有患者中，较高的每日分割剂量240 mg静脉注射控制了AO。对于不能服用口服药物的ZES患者，静脉注射PANTO提供了比现有方法更快速有效地控制AO的显著优势。