Pharmacokinetics of antipyrine, acetaminophen and lidocaine in fed and fasted horses.

This research article explores the changes in the plasma clearance of certain drugs and organic compounds in horses when they are fed and fasted. The study finds that fasting decreases plasma clearance more for organic anions than the drugs under investigation, and that elements other than hepatic blood flow are involved in these reductions.

Research Context and Aim

• The research is built upon the findings from previous studies showing plasma clearance of certain organic anions like bilirubin, bile acid, sulfobromophthalein (BSP), and indocyanine green (ICG), was reduced from 36% to 55% in horses after a 3-day fast.
• The reduction in plasma clearance was initially thought to be due to a general decline in carrier-mediated hepatic uptake. Yet, the role of hepatic blood flow was not ruled out.
• In order to clarify the potential impact of hepatic blood flow and fasting on drug clearance, this study specifically investigates the plasma clearance of antipyrine, acetaminophen, and lidocaine. These drugs are known to be cleared by the liver but are not thought to undergo the same carrier-mediated hepatic uptake.

Research Methodology and Participants

• This research was conducted on nine healthy adult female horses (mares), divided into three groups for each drug test.
• The plasma clearance of antipyrine, acetaminophen, and lidocaine was investigated in these horses before and after a 3-day period of fasting.

Research Findings

• The results show that the fasting caused a more significant decrease in the clearance of organic anions compared to the drugs used in this study (antipyrine, acetaminophen, and lidocaine).
• Interestingly, among the drugs studied, lidocaine, which has the highest plasma clearance and hence was expected to be most affected by reduced hepatic blood flow, was least affected by the fasting.

Conclusion and Implications

• The study concluded that reductions in plasma clearance due to fasting cannot solely be attributed to reductions in hepatic blood flow.
• There must be another factor in play that affects the plasma clearance and drug metabolism, suggesting intrinsic hepatic clearance was reduced as well.
• This work underscores the complexity of how different physiological factors can impact drug metabolism and clearance.