Daily Archives: January 26, 2009

Intranasal Administration of Acetylcholinesterase Inhibitors

The featured paper is ‘Intranasal Administration of Acetylcholinesterase Inhibitors’ by Costantino and colleagues and freely available here. This is a brief review paper. There are a few unusual points. Thus it is an unstructured 3-page review article without a stated methodology and citing 36 references. However there are 5 authors on this paper – 1.6 authors for each page and that includes one page of references! The paper does bring together a number of different disciplines and so it could be argued that different domains of expertise are required in order to lend the article authority. Another unusual point about the paper is that the authors state that there is no conflict of interest. However the stated correspondence address for the authors is given as Nastech Pharmaceutical Company Inc. A cursory examination of the company website (the company is now referred to as mdRNA inc) and other sites reveals a proprietary intranasal delivery system developed by the company with a number of derivative products also being developed. Therefore it can be argued that there is a connection between the company’s products and the current article although it could equally be argued that such an association would not influence the conclusions arrived at within the article.

With regards to the content of the article, the authors consider the benefits of intranasal delivery of drugs. The benefits include bypassing first-pass metabolism in the liver and the ‘large surface’ area. The authors state that ‘this delivery route is non-invasive’. However, after entering the nasal cavity, passing through into the blood-stream and then being conveyed to the brain where its action takes place the case for an ‘invasive’ delivery route can also be argued.

The authors discuss in vivo and in vitro studies of Galantamine. They refer to epithelial tissue preparations where the galantamine’s passage across the cell layer is facilitated by the concurrent delivery of ‘permeation enhancers’ although these are not clarified further within the article. The Galantamine is then tested in vitro with a significant reduction in GI side-effects.  The authors conclude that this is a viable delivery method and that by avoiding GI delivery, the GI side-effects can be avoided.

What I found particularly interesting about this paper is the consideration that the numerous side-effects of a medication can  be further understood by comparing the side-effects resulting from different delivery methods. In this case the evidence would support a direct effect of Galantamine on the GI system in producing the GI effects rather than being secondary to a central effect.

Steps To Treatment 3 (The IN Galantamine would need to be tested in Phase III trials, then gain regulatory approval and then be incorporated into local policy)

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The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.