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Development and evaluation of a novel pharmaceutical dose form for the induction of emesis in canines.

机译：开发和评估新型药物剂型在犬中诱导呕吐。

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摘要

Ingestion of toxic materials continues to be a problem with both humans and canines. Treatment procedures such as emesis have now fallen out of favor largely due to well designed studies in humans which have shown that they are ineffective therapeutically and probably provide no benefit in terms of patient outcome. In veterinary medicine emesis is still used therapeutically in dogs as emesis is somewhat more useful in this species due to differences between human and canine intoxications primarily in terms of the nature of the intoxicant and the quantity consumed. For induction of emesis in dogs, apomorphine is the most appropriate drug but it is generally not used since it has a range of potentially serious dose-related adverse-effects, wide patient variability in terms of response and at present can only be administered by injection. Since the drug can be absorbed by the ocular route, a controlled-release product in the form of an ocular insert was designed, developed and tested. After placement in the eye, apomorphine would be released in a controlled fashion and absorption would occur until emesis is achieved. Further drug absorption would be stopped by removal of the insert so the minimal amount of drug required for emesis would be administered and the occurrence of dose-related adverse effects may be avoided or reduced. In this project, a suitable insert was designed, a method of fabrication developed and the mechanism of release and shelf-life of the product determined. In a clinical trial the insert was shown to induce emesis with an efficacy similar to intravenously administered apomorphine but with a much lower incidence of adverse effects. Although the insert performed well clinically there were some short-comings with the product and several suggestions regarding product improvement are presented.
机译：摄入有毒物质仍然是人类和犬类的问题。呕吐等治疗方法现在已不受欢迎，这在很大程度上是由于对人体进行了精心设计的研究，这些研究表明，它们在治疗上无效，并且可能对患者的治疗效果无济于事。在兽医学上，呕吐仍在犬类中用于治疗，因为在人和犬中毒方面，主要是根据毒物的性质和消耗量的不同，呕吐在该物种中更有用。对于犬呕吐的诱导，阿扑吗啡是最合适的药物，但由于其具有一系列潜在的严重的剂量相关的不良反应，反应广泛的患者变异性，并且目前只能通过注射给药，因此一般不使用。由于药物可以通过眼部途径吸收，因此设计，开发和测试了眼部插入物形式的控释产品。放入眼睛后，阿扑吗啡将以可控的方式释放，吸收会发生，直到出现呕吐为止。通过移除插入物将停止进一步的药物吸收，因此将给予呕吐所需的最小量的药物，并且可以避免或减少剂量相关的副作用的发生。在该项目中，设计了合适的插入物，开发了制造方法，并确定了产品的释放机理和保质期。在一项临床试验中，该插入物可诱发呕吐，其功效类似于静脉内注射的阿扑吗啡，但不良反应的发生率低得多。尽管该插入物在临床上表现良好，但该产品仍有一些缺点，并提出了一些有关产品改进的建议。

著录项

  • 作者

    Cote, Dennis Donald.;

  • 作者单位

    University of Manitoba (Canada).;

  • 授予单位 University of Manitoba (Canada).;
  • 学科 Health Sciences Pharmacy.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 411 p.
  • 总页数 411
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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