Antipyrine and lidocaine are cleared faster in horses than in humans: acetaminophen may be handled similarly.

This research investigated the plasma elimination kinetics of various drugs in horses and humans in an attempt to understand potential species differences in drug metabolization. The study revealed that horses clear certain drugs, such as antipyrine and lidocaine, more rapidly than humans do, while the clearance rate for acetaminophen was similar between the two species.

Study Background and Objectives

• The focus of the research was on the plasma elimination kinetics of three intravenously administered drugs: antipyrine, acetaminophen, and lidocaine.
• The aim was to understand potential differences in drug-metabolizing ability between species, using nine healthy adult horses and nine healthy, drug-free humans as subjects.

Methodology

• The study involved administering each drug to three subjects per species, observing, and analyzing their plasma clearances to infer the hepatic oxidative and conjugative activity related to these drugs.
• In humans, acetaminophen is mainly metabolized in the liver through hepatic glucuronide and sulfate conjugation. Antipyrine and lidocaine, on the other hand, are oxidized by hepatic microsomal mixed-function oxidases.

Results and Findings

• The clearance rate for acetaminophen was found to be similar in both horses and humans.
• Horses cleared antipyrine ten times faster than humans, suggesting enhanced hepatic microsomal activity in horses.
• The humans’ clearance rate for lidocaine was similar to estimated hepatic blood flow, but in horses, the clearance rate was more than double.
• The exceptionally high clearance rate for lidocaine in horses suggests the possibility of metabolism of lidocaine at extrahepatic, extravascular sites.

Conclusion

• The research concludes that horses may have an enhanced ability compared to humans to clear drugs from the circulation that are primarily metabolized in the liver by phase I oxidative reactions, as evidenced by the antipyrine results.