Bioavailability of racemic ketoprofen in healthy horses following rectal administration.

This research investigates the bioavailability of Ketoprofen, a drug used for pain relief in horses, when administered rectally. It finds that the drug’s bioavailability is low, suggesting that a different method of administration could be more effective.

Study Design and Methodology

• The study was conducted using a cross-over design, wherein all participants receive all treatments in different periods. This was a reliable method to compare different ways of administering the same drug (ketoprofen) within the same set of horses.
• The researchers examined the bioavailability of ketoprofen after it was administered in two ways: intravenously (directly into the bloodstream) and rectally, as a suppository. Four healthy horses were used for the study.
• Blood samples were analyzed using high-performance liquid chromatography (HPLC) for ketoprofen enantiomers. Enantiomers are two forms of a molecule that are mirror images of each other. In ketoprofen, these exist as S(+) and R(-) forms.

Findings and Conclusions

• When administered intravenously, the researchers noted that the concentration of the S(+) enantiomer in the horses’ plasma was higher than that of the R(-) enantiomer. This was significant because the same amount of both enantiomers was administered, yet the body absorbed and utilized the S(+) form more.
• The area under the curve (AUC), a measure of the total drug exposure over time, was also significantly higher for the S(+) than for the R(-) enantiomer. This indicates that the S(+) form remained in the body for a longer time interval, hence more effective at producing the desired effect.
• Upon rectal administration, the peak concentration (Cmax) and AUC were again significantly higher for the S(+) than for the R(-) enantiomer, further emphasizing the better uptake of this form of the drug.
• However, the overall bioavailability, or the extent to which the drug reaches the systemic circulation, was low after rectal administration. This is an important finding as it suggests that relatively less of the drug is available to exert its effects when delivered this way, thus possibly affecting its effectiveness.
• The researchers concluded that since there was no significant difference in bioavailability between the two enantiomers, it is likely that no pre-systemic inversion (conversion from one form to another before entering the systemic circulation) from R(-) to S(+) occurred after rectal administration. This effectively rules out the possibility of effectiveness being due to some kind of transformation before absorption.

The implications of this study highlight the need to explore other methods of ketoprofen administration in horses for more optimal drug exposure and efficacy.