Pharmacodynamic properties
Suxibuzone is a Non-Steroidal Anti-inflammatory Drug (NSAID) synthetically derived from pyrazolone with anti-inflammatory, antipyretic and analgesic properties with low ulcerogenic potential.
When mixed with concentrate feed, the product was shown to be palatable to horses. Its mechanism of action is based on the inhibition of the cyclooxygenase (enzyme which catalyzes the synthesis of prostaglandins, prostacyclines and thromboxanes from arachidonic acid). The therapeutic effects are mainly due to the inhibition of the biosynthesis of prostaglandines, which act as peripheral mediators of pain and trigger the synthesis of endogen pyrogens and mediators in the inflammatory process. It also inhibits platelet aggregation.
The therapeutic effect of suxibuzone relies entirely on the activity of its active metabolites. Strong anti-inflammatory activity has been shown for phenylbutazone and oxyphenbutazone. The third metabolite gamma-hydroxyphenbutazone is considered to be pharmacologically inactive.
Pharmacokinetic particulars
After oral administration suxibuzone is readily absorbed and most of it is metabolised by the hepatic microsomal system producing phenylbutazone, oxyphenbutazone and gamma-hydroxyphenylbutazone. No unaltered parent compound can be detected in plasma after oral administration of suxibuzone to horses. These active metabolites have a high degree of affinity for plasma proteins and are eliminated mainly through urine, as glucoronide conjugates, but also, in a small percentage, through faeces. Less than 1% is eliminated through saliva and milk.
After the administration of a single 6.25 mg/kg oral dose of the parent compound phenylbutazone reaches its maximum plasma concentration (9.9±2.3 μg/ml) at 11±3 hours after administration with an elimination half life of 7.1±0.5 h. Oxyphenbutazone reaches its maximum (1.5±0.4 μg/ml) at 15±5 hours after administration.
As happens with other NSAID´s the duration of the clinical response is much longer than the plasma half-life. Significant concentrations of both active metabolites are found in synovial fluid for at least 24 hours after administration.