Leukemia Drug Adulteration
Chinese generic versions of the anticancer drugs, methotrexate and cytarabine hydrochloride, have been reported to be contaminated with an undisclosed substance according to several wire reports this morning.
Several children in a Shanghai hospital were reported to suffer leg pain and difficulty walking after being injected with methotrexate. A common drug used in many chemotherapy regimens for leukemia, methotrexate is not normally associated with these side effects.
The Xinhua news agency reported that the drugs had been traced to one manufacturer, Shanghai Hualian Pharmaceutical Co. The report also noted the Chinese government had suspended manufacture and sale of these two drugs earlier this month. I was unable to find details on the unexpected side effects of cytarabine, another antileukemia drug, but I infer from the AP reports that the leg pain was also the signal something was wrong with that drug preparation. No information was provided as to whether any of the offending products were exported to other countries.
China has been suffering a great deal of bad publicity over tainted products exported to other countries, such as toothpaste contaminated with diethylene glycol and toys finished with lead-based paint.
The Ractopamine Pig Wars and a Pharmacology Lesson
But in a report I missed, the Chinese noted that they have also been subject to adulterations of imported US and Canadian pork that contained the growth stimulant, ractopamine. While the Chinese are reported to have a "zero-tolerance" policy to this growth stimulant, British-based ThePigSite.com reported last month that the ractopamine had also been detected in Chinese domestic pork as well. (FYI, the EU also forbids ractopamine use in livestock.).
In preparing the following quick pharmacology lesson on ractopamine (for myself as much as for readers), I was prompted to give thought to the health of farm workers who might handle the product.
Ractopamine is sold in the US under the brandname, Paylean®, by Elanco, a division of the pharmaceutical giant, Eli Lilly and Company. The compound is not a steroid but acts as predominantly as an agonist (or stimulator) of the adrenergic β2 receptor to cause reduced fat deposition and increased lean muscle mass in swine when given for the final 28 days prior to slaughter (or "barn closeout" as they say in the biz).
For comparison, agonists of the same β2 receptor like albuterol are used in humans to prevent or reverse the airway constriction of asthma. Animal science researchers at Purdue have reported that ractopamine also is a partial agonist at the β1 receptor, the same receptor that we try to block with the antihypertensive, atenolol (Tenormin®).
So, would Paylean® cause pigs to become hypertensive prior to slaughter. The label does at least state that, "Ractopamine may increase the number of injured and/or fatigued pigs during marketing."
Another concern is what might ractopamine do to agricultural workers who handle it?
In defense of Elanco, the label for Paylean® (PDF here) does note that people with cardiovascular disease should exercise "special caution" in handling the product, particularly to avoid inhalation of the powder.
This discussion is not merely an intellectual exercise. We have seen over the last few years, perhaps even as early as 1985, that workers in microwave popcorn plants have been experiencing irreversible lung damage (broncholitis obliterans) due to inhalation of the butter flavoring agent, diacetyl (or 2,3-butanedione). The Pump Handle blog also recently broke the story of the first consumer with the same type of lung damage due to inhaling the vapors of freshly-microwaved popcorn.
What we do in manufacturing our food does indeed matter - no just to the consumer, but to those who labor to put food on our tables.
Nice piece, Abel. I shudder to think where we'd be without the ongoing work done by FDA and similar independent regulatory agencies ... to help protect us from errors and misdeeds.
Umm, Abel Pharmboy, you've made a mistake.
For comparison, antagonists or blockers of the same β2 receptor like albuterol are used in humans to prevent or reverse the airway constriction of asthma;
Albuterol (Salbutamol) is a β2 receptor agonist. This doesn't mean that people with asthma should be cavalier about using ractopamine, it might be additive with their standard medications and potentially cause overdose, but they are very unlikely to get an asthma attack from it.
The Paylean(c) handout does state that protective clothing, googles and dust masks should be used, with washing after (although the likelyhood of all farmers following these recomendations is low). Still, the possibility potential interactions with asthma medication should be mentioned.
Well, the same Purdue animal sciences group has shown that some adrenergic compounds bind to pig β2 receptors 10-50 times more tightly
Yes, but these are ones with β-hydroxypropanolamine structures. Drugs structurally related to ractopamine (phenylethanolamines such as isoproterenol, BRL 37344, etc.) all had pretty similar affinities between human and pig receptors, so it would be wise to treat ractopamine as equally efficacious at human β2 receptors.
Dr Musgrave, many thanks for catching the mistake; I take albuterol so I should know better. This makes me recall that early beta-blockers like propranolol were contraindicated in asthma patients because of their lack of antagonist selectivity for β1 vs. β2 receptors. The post has been corrected.
No problem Abel, thanks fro the prompt response (and an interesting and topical post). Many thanks for your thoughtful posts in general, I often point my students your way in matters of natural products.