Effects of oral cimetidine on plasma concentrations of phenylbutazone in horses.

This research investigates the impact of the drug cimetidine on blood levels of phenylbutazone in Thoroughbred horses, finding that pre-treating horses with cimetidine increases the plasma concentrations and absorption rate of phenylbutazone in the first 8 hours following administration but does not affect phenylbutazone levels after 24 hours.

Study Design

• The experiment adopted a cross-over study design involving six Thoroughbred horses. In a cross-over study, each participant receives both the treatment and control conditions in random order, which allows each horse to act as its own control, increasing the accuracy of the results.
• Each horse was either pre-treated with cimetidine or not pre-treated at all before being given phenylbutazone. This means that there were two conditions in the study: a ‘control’ condition without any cimetidine pretreatment and a ‘treatment’ condition in which horses were pre-treated with cimetidine.

Data Collection

• Blood samples from horses were collected at various intervals in the 48 hours following phenylbutazone administration.
• The blood plasma was then analyzed to measure the concentration of phenylbutazone, as well as its metabolites gamma-hydroxyphenylbutazone and oxyphenbutazone.

Findings

• The pretreatment with cimetidine was found to increase the plasma concentration of phenylbutazone in horses for the first 8 hours after the phenylbutazone was administered.
• The absorption and maximum plasma concentrations of phenylbutazone were found to be significantly greater when horses were pre-treated with cimetidine.
• However, the half-life of phenylbutazone remained unaffected by cimetidine pretreatment. This means that cimetidine did not significantly change the time taken for the concentration of phenylbutazone in plasma to reduce by half.
• Moreover, lower plasma concentrations of the metabolite gamma-hydroxyphenylbutazone were observed when the horses were pre-treated with cimetidine, although the concentration of another metabolite, oxyphenbutazone, remained unchanged.
• After 24 hours, the plasma concentrations of phenylbutazone were seen to return to control values (i.e., the levels seen in horses not pre-treated with cimetidine).

Conclusion

• The results suggest that while co-administration of cimetidine and phenylbutazone does increase phenylbutazone concentrations in the short-term (first 8 hours), it does not result in longer-term elevations of plasma phenylbutazone concentrations (past 24 hours).