Sykes B W, Kathawala K, Song Y, Garg S, Page S W, Underwood C, Mills P C
School of Veterinary Science, University of Queensland, Gatton, Queensland, Australia.
Luoda Pharma Pty Ltd, Caringbah, New South Wales, Australia.
Equine Vet J. 2017 Nov;49(6):795-801. doi: 10.1111/evj.12688. Epub 2017 May 17.
Pilot investigations have suggested that a novel, long-acting, injectable i.m. formulation of omeprazole (LA-OMEP) can induce acid suppression for up to 7 days following a single injection.
To investigate the pharmacodynamics and assess the clinical efficacy of the LA-OMEP formulation.
Part A comprised a pharmacodynamic study. Part B consisted of a pilot clinical trial.
Part A enrolled six adult Thoroughbred horses with percutaneous gastrotomy tubes. Intragastric pH was measured for continuous 23-h periods (08.00-07.00 h) for eight consecutive days (days 0-7). A single 2.0-g dose of a 100 mg/mL LA-OMEP formulation was administered at 08.00 h on day 1. In Part B, 26 horses with squamous or glandular gastric disease were enrolled based on routine gastroscopic evaluation. Once enrolled, horses received 2.0 g of the 100 mg/mL LA-OMEP formulation by i.m. injection on days 0 and 7. Repeat gastroscopy was performed on days 14 (23 horses) or 16 (one horse).
In Part A, the percentage of time during which pH was above 4 exceeded 66% for days 1-4 in all horses and days 1-7 in four of the six horses studied. In Part B, healing was observed in all 22 (100%, 95% confidence interval [CI] 89-100%) horses with squamous disease and in nine of 12 (75%, 95% CI 47-92%) horses with glandular disease. Improvement, by at least one grade, was observed in all 22 (100%, 95% CI 89-100%) horses with squamous disease and in all 12 (100%, 95% CI 81-100%) horses with glandular disease. No worsening of lesions was observed. Lesion grade decreased over time in both the squamous (P<0.0001) and glandular (P = 0.0024) mucosa.
Small sample sizes.
The results of the present study compare favourably with previous reports on the pharmacodynamics of omeprazole and the clinical outcomes of trials reporting response to oral omeprazole therapy.
初步研究表明，一种新型长效注射用奥美拉唑（LA-OMEP）肌内注射制剂单次注射后可诱导胃酸抑制长达7天。
研究LA-OMEP制剂的药效学并评估其临床疗效。
A部分为药效学研究。B部分为初步临床试验。
A部分纳入了6匹成年纯种马，这些马均经皮插入胃造瘘管。连续8天（第0 - 7天）每天在23小时内（08:00 - 07:00）测量胃内pH值。在第1天08:00给予单剂量2.0 g的100 mg/mL LA-OMEP制剂。在B部分，根据常规胃镜检查评估，纳入26匹患有鳞状或腺性胃部疾病的马。一旦纳入研究，这些马在第0天和第7天通过肌内注射给予2.0 g的100 mg/mL LA-OMEP制剂。在第14天（23匹马）或第16天（1匹马）进行重复胃镜检查。
在A部分，所有马匹在第1 - 4天以及6匹研究马匹中的4匹在第1 - 7天，pH值高于4的时间百分比超过66%。在B部分，所有22匹（100%，95%置信区间[CI] 89 - 100%）患有鳞状疾病的马以及12匹患有腺性疾病的马中的9匹（75%，95% CI 47 - 92%）观察到愈合。所有22匹（100%，95% CI 89 - 100%）患有鳞状疾病的马以及所有12匹（100%，95% CI 81 - 100%）患有腺性疾病的马均观察到至少改善一个等级。未观察到病变恶化。鳞状（P<0.0001）和腺性（P = 0.0024）黏膜的病变等级均随时间下降。
样本量小。
本研究结果与先前关于奥美拉唑药效学以及报告口服奥美拉唑治疗反应的试验临床结果的报告相比具有优势。
