Talk:Tenofovir disoproxil

Wiki Education Foundation-supported course assignment

This article is or was the subject of a Wiki Education Foundation-supported course assignment. Further details are available on the course page. Student editor(s): Merctang, Sarahsana, Laneyluong, Ktham. Peer reviewers: Bsalce, Swani8, Gloring14, Stephanie.eg.

Above undated message substituted from Template:Dashboard.wikiedu.org assignment by PrimeBOT (talk) 10:51, 17 January 2022 (UTC)

removal of section

The section on increased yield seems superfluous. as dasd asd

My opinion as well. It doesn't add much useful to the article.

It was added in 2011 [1] by User:Nbauman.

And it is not even changed a lot from the original article in the Wall Street Journal:

"A difficult step in the manufacture of tenofovir is near the end, when the mixture is "like oatmeal, making it very difficult to stir," said Joseph Fortunak, who left Abbott Laboratories to teach at Howard. That slows the next reaction, a problem because the intermediary is highly unstable and decomposing, lowering the yield. Fortunak's graduate student Adrian Williams tested different methods to improve this step. A catalyst, TBAB (tetrabutylammonium bromide) sped up the reaction and thinned the oatmeal-like mixture into something "like milk," Williams said. But unexpectedly, it made the product more stable, which substantially increased the yield. This lowered the cost by about 20%."

Compared to the cited article:

"A particularly difficult step in the manufacture of the antiretroviral drug tenofovir comes near the end. The mixture at that point is "like oatmeal, making it very difficult to stir," explained Prof. Fortunak. That slows the next reaction, a problem because the substance that will become the drug is highly unstable and decomposing, sharply lowering the yield. One of Prof. Fortunak's graduate students, Adrian Williams, painstakingly tested many possible methods to improve this step. His eureka moment came when he added a catalyst known as TBAB, short for tetrabutylammonium bromide. TBAB sped up the reaction and thinned the oatmeal-like mixture into something "like milk," Mr. Williams said. But, said Prof. Fortunak, "the really unexpected thing was it made the product more stable—this we did not expect at all." The result was a substantial increase in yield." Peterthewall (talk) 07:18, 21 May 2014 (UTC)

Whether it's superfluous depends on whether you think pharmaceutical chemistry is important. I've talked to research pharmacists who described other similar problems with scaling products up and bringing them to market. It's an important example of the problems that come up in pharmaceutical development, and how they're solved. A change that lowers the cost 20% is significant.

When you are summarizing another source, you can only change so much and still summarize accurately. I challenge you to change that paragraph and not delete or alter significant information. --Nbauman (talk) 02:41, 23 May 2014 (UTC)

As a chemist, I've always been skeptical of that paragraph. In my experience this sort of eureka moment happens at least once in every new synthesis, as seemingly unsolvable problems are overcome through dilligent research. So I don't see it as notable, especially as this particular problem was solved by switching from one well kniwn reagent to another. Also we have no citation showing that this method is used for industrial scale production.Formerly 98 (talk) 13:18, 23 May 2014 (UTC)

The source is the Wall Street Journal, which is a WP:RS. I'm not sure that a detail like that would be reported in the scientific literature, although you're welcome to look in a database for confirmation. The WSJ reporter thought it was notable, and the researchers in describing it to the reporter thought it was notable. Yes, it's the kind of eureka moment that happens in every new synthesis, through dilligent research. That's the point. It illustrates how pharmaceutical chemistry works, with an example that even a non-chemist can understand. --Nbauman (talk) 03:43, 2 June 2014 (UTC)

Chemistry is every bit as much a technical field as medicine, and we don't accept the WSJ as a reliable source for medical information. In fact, I'd say my experience has been that the popular press gets chemistry wrong a higher fraction of the time than they get medicine wrong.

Gilead does not use that method because they would have to submit a completely new NDA with the new impurities from the changed synthetic route all characterized. Cipla said they don't use it, and so did Mylan. Aptuit's remarks are ambiguous. For this to be notable, at a bare minimum someone has to be using it, and the WSJ article does not establish that. Nor do we discuss the methods used by Gilead, Cipla, and Mylan to solve this same problem in the article.

I realize that anyone in this anonymous environment can claim anything, but if you'll take my work for it, I'm a PhD chemist with 15 years experience in the industry. This is not a notable discovery in my opinion. Its just been hyped. There is reasonable evidence that the pharmaceutical industry as a whole was not hugely impressed by this accomplishment. Although Mr. Williams was reportedly finished with his dissertation at the time this article published 3 years ago and looking for work at a pharmaceutical company, there are no patent applications at the USPTO on which he is listed as an inventor, and no papers under his name listed at Pubmed. If this work was that impressive, He should have been snapped up quickly and have at least 3-4 patents and publications out by now.

Here's how Gilead did it by the way. Lots of ways to skin a cat. https://www.google.com/patents/US6465649?dq=6,465,649&hl=en&sa=X&ei=qgWMU6WAPYa6oQTL_oKYDA&ved=0CCgQ6AEwAA

Formerly 98 (talk) 04:56, 2 June 2014 (UTC)

Tenofovir disoproxil fumarate vs. "tenofovir"

The situation is a little confusing here, but I think the chemical structure should match that of the clinically used drug.

• Tenofovir is the active form of the drug in tissues. Tenofovir disoproxil fumarate is its prodrug.
• Tenofovir itself is not marketed as a drug anywhere in the world. It is not orally absorbed because of the two negative charges of the phosphate group at the pH of the GI tract
• The world "tenofovir" is colloquially used as shorthand for tenofovir disoproxil fumarate.

So its complicated, but I think the chemical structure shown should correpond to the approved drug. We generally have articles titled to the marketed product, and not its active metabolite.

That being said, the structure and title should match. I'd suggests to use the strucuture of the approved drug and change the article title from the colloquial "tenofovir" to the approved drug's USAN name, tenofovir disoproxil fumarate.

Tenofovir alafenamide fumarate is a different prodrug in development. It has different pharmacokinetics, and appears to have a different side effect profile as well. It will likely need its own article, so maybe best that this one focus on the disproxil prodrug and not the active drug in tissues. 73.162.132.47 (talk) 10:43, 24 November 2015 (UTC)

Hi, and thanks for your input and clarification. So,

1. tenofovir is the active metabolite, and I agree that the article should not be about it,
2. tenofovir disoproxil fumarate is the salt of the prodrug, and this shouldn't be the article's title either (just as we don't have "Diclofenac sodium" but "Diclofenac" etc., see WP:MOSPHARM),
3. tenofovir disoproxil is the active moiety (in the sense of WP:MOSPHARM) after which this article should be named.

By the way, however this turns out, drugboxes should be about a single chemical entity. Currently, the chemical identifiers, molecular mass etc. are about tenofovir, the KEGG identifier is the one of the fumarate, and both structures are given; this is confusing. I'd not be opposed to having two drugboxes (tenofovir disoproxil anf tenofovir itself), but I don't think the fumarate should be in it per the above reasoning. Cheers, --ἀνυπόδητος (talk) 11:26, 24 November 2015 (UTC)

Agree with all of the above. 73.162.132.47 (talk) 19:03, 25 November 2015 (UTC)

The common name however is tenofovir. Do not see an issue either way. Doc James (talk · contribs · email) 11:19, 27 November 2015 (UTC)

I'd say the "use INN" rule takes precedence over WP:COMMONNAME, especially as tenofovir is chemically different. Calling TDF "tenofovir" is common, but jargon. --ἀνυπόδητος (talk) 11:23, 27 November 2015 (UTC)

Yes agree the INN should take precedence. Thks Doc James (talk · contribs · email) 12:05, 27 November 2015 (UTC)

@Anypodetos and Doc James: The box for "Tenofovir disoproxil" is still messed up. The chemical formula is for the fumarate, and the fumarate is also given after "Other names". I haven't check'd all of the "Identifiers", but at least the "CAS Number" refers to the base without the fumaric acid. Eric Kvaalen (talk) 12:48, 21 August 2021 (UTC)

Thanks; I fixed all the errors I could find. The formula seems to be correct, though (not the fumarate). --ἀνυπόδητος (talk) 19:26, 21 August 2021 (UTC)

Wiki Project Plan of Action

Our plan to improve the Tenofovir page:

• Introduction: Will make the introduction a 3-4 paragraph lead with summarized information. Will include pertinent information such as class, side effects, costs, indication, mechanism of action, and relevant history.
• Medical Uses: Will adjust formatting. Include an overview of treatments using Tenofovir before putting more in depth information.
• Adverse Effects: Improve citations. Will remove primary source and single-study information.
• Interactions: Will investigate about interactions with Tenofovir with emphasis on medications that are often used in combination for treatments.
• Pharmacology: Will try to improve comprehension with lay language.
• Pharmacokinetics: Will check sources and only include confirmed facts. Will try to find English sources for the English Wikipedia.
• Drug forms: Will update on available forms.
• Chemistry: Will consider the role of this section in reference to the individuals who may access the page. Will try to improve on lay language and link to sources of complicated topics such as liquid chromatography.

Merctang (talk) 18:48, 3 November 2016 (UTC)

Peer Review 2016

STUDENT 1 - "Does the draft submission reflect a neutral point of view? If not, specify…" After reviewing the Wiki page I believe that the submission is from a neutral point of view. It does nothing to promote or defame Tenofovir. It comes from a stance of delivering unbiased knowledge that allows the person reading the article to make their own decision. Bsalce (talk) —Preceding undated comment added 23:08, 15 November 2016 (UTC)

STUDENT 3 – Are the edits formatted consistent with Wikipedia’s manual of style for medicine-related articles? If not, specify… After review of the article, the edits are consistent with Wikipedia's manual of style for medicine-related articles. Medical jargon is explained, and it appears to be readable by a non-health professional (ex: using the word "kidney" instead of "renal"). Gloring14 (talk) 17:26, 15 November 2016 (UTC)

STUDENT 2 – "Are the points included verifiable with cited secondary sources that are freely accessible? If not, specify.." Yes, After reviewing the citations that were used throughout the Wikipedia page for Tenofovir you can see that the group did in fact used secondary sources such as "Medline Plus Articles". Medline Plus is a source that was throughout our sourcing class was stated to be a good resource to use for this assignment. Also, it is easily accessible to the public. Another source that was used was the pharmaceutical companies PI for the drug itself which is also a source that can be easily attained online. Stephanie.eg (talk) 19:47, 15 November 2016 (UTC)

STUDENT 4 - "Is there any evidence of plagiarism or copyright violation? If yes, specify…" There is no evidence of plagiarism or copyright violation. Each section is cited properly and thoroughly. Wording has been changed from the original source as well. Overall, good work! — Preceding unsigned comment added by Swani8 (talk • contribs) 20:44, 15 November 2016 (UTC)