S P E C I A L R E P O R T
Written and Researched by JANE ALLIN
“BUTE” is by no means the only drug under scrutiny in the sport horse and racing industry however its metabolic activity and "decay life" in animal tissue is in direct contrast to many other legally permissible medications which are transient in nature and are biologically eliminated from the system over established intervals.
Of particular note however is the fact that “bute” is the most widespread anti-inflammatory in the global horse racing industry today. It is estimated that 98% of NA professional sport and pleasure horses have received phenylbutazone at some point in their lives and is widely used in other horse industry jurisdictions around the globe.
The kinetics and drug activity of phenylbutazone and its metabolites (e.g. oxyphenbutazone) are characteristic of a bi-exponential decay rate (the sum of two single exponential decays) meaning, in theory, that regardless of the elapsed time there will always be residuals present in blood plasma (i.e. the concept of infinite division). 
An exponential decay rate can be expressed in terms of "half-life" where one half-life represents the amount of time it takes for the substance undergoing "decay" to decrease by one half of the original concentration. Half-lives remain constant over the decay period and as the concentration approaches zero, the time to eliminate any residuals remaining in the system approaches infinity. In other words, there will always be some residuals present regardless of the passage of time.
Table 1 and Figure 1 together illustrate a simple model of exponential decay.
Of particular note is that regardless of the number of half-lives denoted by "n", the fraction or percentage of the original concentration of the substance under analysis will always be greater than zero.
Table 1: Exponential Decay Concept
Where n = number of half-lives
Figure 1: Exponential Decay Curve Showing Persistence of Residues
Decades ago phenylbutazone, a compound originally used in Europe as a solubilizing agent for various analgesics given by intramuscular injection, was introduced to the drug compendium in the US for the treatment of rheumatoid arthritis and gout, nonetheless with fateful brevity.
Admitted in 1949, and shortly thereafter banned by the FDA for human use, by the year 2003 the ban extended to animals intended for human consumption given that investigation by FDA and State regulatory counterparts determined that phenylbutazone residues were discovered in culled dairy cattle.  
At the time this did not include horses or dogs as in North America neither are considered food animals.
"Phenylbutazone (PBZ) was marketed in the United States for the treatment of rheumatoid arthritis and gout in 1952. Serious and often fatal adverse effects such as aplastic anemia and agranulocytosis appeared in the literature within three years of its use . . . . . The serious adverse effects of PBZ culminated in its unavailability for human use in the United States." 
Apart from aplastic anemia (bone marrow suppression) and agranulocytosis (reduction in infection fighting white blood cells), phenylbutazone and its principal metabolite oxyphenbutazone have also been implicated in thrombocytopenia (low platelet count), leucopenia (decreased white blood cells), pancytopenia (reduced red and white blood cells and platelets), hemolytic anemia (abnormal breakdown of red blood cells) and can cause hypersensitivity reactions in the liver leading to death. 
Moreover, phenylbutazone is a carcinogen, as determined by the National Toxicology Program. 
Clearly there is apt rationale for banning phenylbutazone for human use as well as animals intended for human consumption both as a function of its toxicity and the causal certainty that residues will always be present to some extent in the blood and hence tissues of animals slaughtered for food.
Additionally, what is most disconcerting is that the lethal adverse effects in humans are not always dose-dependent and demonstrate unique outcomes contingent on a particular individual’s susceptibility. In essence what this implies is that even in small quantities phenylbutazone and its metabolites can have deleterious effects on human health. 
To this end, the FDA has banned the use of phenylbutazone in horses destined for slaughter.
Moreover, there are no farming associations that raise horses for food in North America (unless the AQHA can be considered eligible). And despite the fact that horse slaughter in the US has been outlawed since 2007, there is no pretense about what happens to more than 100,000 horses sold annually at auction who are shipped to Canada and Mexico. Once butchered, their meat is exported to European and Asian locales where it fetches top dollar and is considered a delicacy.
The fact is that the majority of these horses will be administered phenylbutazone during some point in their lives to relieve musculoskeletal pain and inflammation.
This in itself is not entirely inappropriate as there are valid reasons for its use in the treatment of lameness providing the recommended dosage is abided by, as there are also potential life-threatening side-effects to the horse (e.g. severe gastric ulceration).
Instead, the glaring inconsistency is the unmistakable fact that these horses enter the food chain; perhaps not in North America but elsewhere through export to foreign countries nonetheless. What’s more, since the residues of phenylbutazone and its metabolites reside primarily in the blood plasma of the tissues there is the complicating factor of the inherent differences between slaughtered cattle and horse carcasses.
"As stated above, almost all of the PBZ remains in the bloodstream. . . . To provide a point of comparison, a 1400 lb cow has 60 ml/kg body weight or almost 10 gallons or 0.71 gallons per 100 lbs of cow. The ratio is 1.25/.71 = 1.76:1. Thus, a horse has 1.76 times as much blood per pound of body weight compared to a cow."
Potentially this means that there is a calculated measure of risk of the presence of higher concentrations of toxic residues in horse meat than in beef. In actual fact there is no "risk" of higher concentrations in horse meat in light of the fact that the drug has been banned in other animals, such as cattle for example, intended for human consumption since 2003: the residues are undeniably higher in horse meat. Still the quandary exists.
"The FDA, like the EU and UK, specifically bans the use of PBZ in any horse destined for slaughter for human consumption. Yet, this ban is being circumvented because there is no pre-slaughter mechanism to determine and remove horses that receive PBZ during their lifetime. This is because horses are not regarded as or treated as food-producing animals in the United States and there are no USDA regulations to prevent them from being given banned substances like PBZ." 
Horses may not be perceived as food-producing animals in the US, but they are certainly treated as if they are, in the same appalling manner.
 Ibid at 1.
 Ibid at 1.
 Ibid at 1.
 Ibid at 1.
 Ibid at 1.