{"id":526,"date":"2013-02-19T15:56:59","date_gmt":"2013-02-19T15:56:59","guid":{"rendered":"http:\/\/occamstypewriter.org\/irregulars\/?p=526"},"modified":"2013-02-19T15:56:59","modified_gmt":"2013-02-19T15:56:59","slug":"the-bute-in-horsemeat","status":"publish","type":"post","link":"https:\/\/occamstypewriter.org\/irregulars\/2013\/02\/19\/the-bute-in-horsemeat\/","title":{"rendered":"The \u201cbute\u201d in horsemeat"},"content":{"rendered":"

The horsemeat scandal in Europe continues to surprise and shock.\u00a0 Henry Gee has written about the controversy for this site<\/a> and for Occam\u2019s Corner<\/a> but I wanted to comment on one of the safety issues.<\/p>\n

It seems that a drug, colloquially known as \u201cbute\u201d, has entered the human food chain via some of the horsemeat produced in the UK.\u00a0 This revelation piqued my pharmacological interest.\u00a0 I wasn\u2019t familiar with \u201cbute\u201d or to give it its proper chemical name, phenylbutazone, so I decided to dig around a bit.<\/p>\n

Quite quickly I found that phenylbutazone had been marketed for human use under the trade name of butazolidine. For me, hearing this name was Proustian, and I was transported back more than 40 years to my father\u2019s pharmacy.\u00a0 As a teenager, I would occasionally help him dispense drugs and I well remember counting out butazolidine tablets all those years ago.\u00a0 In those days, blister packs did not exist; there were large bottles of tablets in the dispensary and it was the job of the pharmacist to transfer the correct number to a small, carefully labelled glass bottle.<\/p>\n

This anecdote is part of my history but it does tell us one thing: phenylbutazone is an old drug.\u00a0 In fact it was first synthesised by Geigy Pharmaceuticals in Basel and marketed as butazolidine in the late 1940\u2019s. \u00a0\u00a0The drug was used to treat arthritis and other painful inflammatory conditions and for patients that tolerated the drug it was an effective remedy.\u00a0 It is classified as a Non Steroidal Anti-inflammatory Drug (NSAID), a class of drugs widely used to treat pain and inflammation.\u00a0 \u00a0Aspirin was the first NSAID and many people will be familiar with ibuprofen, another member of this group of drugs. \u00a0NSAIDs relieve pain and inflammation by inhibiting an enzyme that synthesises chemical mediators called prostaglandins.<\/p>\n

Whereas aspirin and ibuprofen are quite well tolerated by patients, the use of phenylbutazone was associated with a wide range of side effects.\u00a0 The most serious of these were blood dyscrasias where bone marrow production of blood cells was affected.\u00a0 This disorder was fatal for about 1 in 45000 of patients taking the drug.\u00a0 More than a quarter of patients taking the drug reported other side effects including gastrointestinal bleeding, oedema, and toxic effects on the liver or kidney.<\/p>\n

By the mid 1980\u2019s, phenylbutazone was withdrawn from general use, partly because of the side effects and partly because better drugs such as ibuprofen had appeared on the market.\u00a0 Phenylbutazone still features in the British National Formulary as a treatment for the severe rheumatic disorder ankylosing spondylitis, but for use only when other drugs are unsuitable.<\/p>\n

Despite being withdrawn for general human use, the drug has found a niche in veterinary medicine where it is widely used to treat pain and inflammation in horses.\u00a0 Although horses treated with phenylbutazone are not supposed to enter the human food chain, it seems that this rule has been flouted in some cases.\u00a0 The drug has been found recently in horses slaughtered in the UK but destined for human consumption in continental Europe.<\/p>\n

The question then is whether this poses a risk to human health so we need to know the levels of drug found in the horsemeat.\u00a0 The most straightforward way to express the levels of phenylbutazone is to work out how much there is in a kilo of the meat and in the recent tests, the highest amount found was 1.9 mg.\u00a0 The Chief Medical Officer, Dame Sally Davies has said that this level of phenylbutazone poses no risk to human health and I thought it might be useful to think about how this conclusion was reached.\u00a0 In the past, when phenylbutazone was used in patients, a typical dose would have been 400 mg a day, spaced out in four equal amounts.\u00a0 To reach this level you would need to eat as much as 200 kilos of contaminated horsemeat a day!\u00a0\u00a0 On that basis there would appear to be little or no risk.<\/p>\n

 <\/p>\n

I wonder, however, if there is a bit more complexity to the story and here are some issues that give me pause for thought:<\/p>\n

    \n
  1. \u00a0The argument about the levels of phenylbutazone in horsemeat assumes that it would be necessary to consume up to 400 mg a day of the drug to see effects.\u00a0 The relation between drug dose and drug response is, however, a complex one, especially for phenylbutazone. I don\u2019t know whether 400 mg of drug is just enough to give a response or whether it is well over that level.\u00a0 If the latter is true, then lower amounts of drug might have small effects.<\/li>\n
  2. Some drugs are said to interact so that the effects of one drug on a patient may be modified if they also take a second drug.\u00a0 There is a very well known interaction between phenylbutazone and the anticoagulant drug warfarin and patients taking warfarin can suffer severe gastrointestinal bleeding if they also take phenylbutazone.\u00a0 The mechanism of this interaction is complex and, as far as I can tell, it is not fully understood.\u00a0 This complicates arguments about safety of phenylbutazone in horsemeat.<\/li>\n
  3. Phenylbutazone is broken down in animals and in humans to another drug called oxyphenbutazone.\u00a0 This has many of the same actions as phenylbutazone and I wonder if oxyphenbutazone has been tested for in the horsemeat.<\/li>\n
  4. Drugs developed nowadays are very well characterised for potential side effects and off-target interactions. \u00a0Because phenylbutazone was developed so long ago, it will not have been characterised in the same way.\u00a0 I doubt if we know all the potential actions of the drug.\u00a0 If any of these occurs at lower concentrations than the effects on pain and inflammation, this could complicate arguments about safety.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    The horsemeat scandal in Europe continues to surprise and shock.\u00a0 Henry Gee has written about the controversy for this site and for Occam\u2019s Corner but I wanted to comment on one of the safety issues. It seems that a drug, … Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":153,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[20,1],"tags":[146,143,145,141,144,142],"class_list":["post-526","post","type-post","status-publish","format-standard","hentry","category-guestposts","category-uncategorized","tag-butazolidine","tag-bute","tag-bute-in-horsemeat","tag-horsemeat","tag-human-consumption-of-horsemeat","tag-phenylbutazone"],"_links":{"self":[{"href":"https:\/\/occamstypewriter.org\/irregulars\/wp-json\/wp\/v2\/posts\/526","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/occamstypewriter.org\/irregulars\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/occamstypewriter.org\/irregulars\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/occamstypewriter.org\/irregulars\/wp-json\/wp\/v2\/users\/153"}],"replies":[{"embeddable":true,"href":"https:\/\/occamstypewriter.org\/irregulars\/wp-json\/wp\/v2\/comments?post=526"}],"version-history":[{"count":0,"href":"https:\/\/occamstypewriter.org\/irregulars\/wp-json\/wp\/v2\/posts\/526\/revisions"}],"wp:attachment":[{"href":"https:\/\/occamstypewriter.org\/irregulars\/wp-json\/wp\/v2\/media?parent=526"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/occamstypewriter.org\/irregulars\/wp-json\/wp\/v2\/categories?post=526"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/occamstypewriter.org\/irregulars\/wp-json\/wp\/v2\/tags?post=526"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}