Pharmacokinetic interactions between repeated dose phenylbutazone and gentamicin in the horse.

The research investigates how the combination of phenylbutazone and gentamicin, two medications, interacts within the body of a horse. Specifically, it was found that when administered together, phenylbutazone altered the distribution and elimination rates of gentamicin.

Research Design and Methodology

• In this research, a cross-over trial design was utilized with seven thoroughbred horses. This means each horse served as its own control, receiving both the treatment (combination of phenylbutazone and gentamicin) and comparing it to a baseline (gentamicin alone).
• In the first phase, each horse was given a single intravenous dosage of gentamicin, followed by a two-week period (or washout) to allow any residual effects of the drug to wear off.
• After this break, each horse was given doses of phenylbutazone every 24 hours for 5 days. On the fourth day of this cycle, they received gentamicin as in the first phase.
• The researchers used plasma samples to determine the concentration of both phenylbutazone and gentamicin in the body of the horse, using high-performance liquid chromatography for phenylbutazone and a fluorescence polarization immunoassay for gentamicin.

Findings and Analysis

• The data for gentamicin were best approximated using a two-compartment open model, using sequential, weighted non-linear regression. This is a common model used in pharmacokinetic studies to indicate the absorption and distribution of a substance.
• The results showed that phenylbutazone caused a significant increase in the speed at which gentamicin was returned to the central compartment of the body from peripheral tissues. Additionally, there was a trend towards an increase in the rate at which gentamicin moved from the central compartment to the peripheral tissues.
• The half-life of gentamicin, meaning the time it takes for the concentration of the drug to be reduced by half, was decreased by 23% when administered with phenylbutazone. Moreover, the volume of distribution (Vd) was reduced by 26%.
• Interestingly, no changes were observed in the pharmacokinetics of phenylbutazone due to gentamicin.

Conclusion

• The study concludes by suggesting caution when using aminoglycosides, such as gentamicin, in horses that are already being treated with phenylbutazone. This is due to the finding that phenylbutazone alters the rate of distribution and elimination of gentamicin in the body.