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

Abstract

Previous studies demonstrated that plasma clearance of organic anions such as bilirubin, bile acid, sulfobromophthalein (BSP) and indocyanine green (ICG), was reduced from 36% (bile acid) to 55% (ICG) in fasted (3 days) horses. It is believed that a general decline in carrier-mediated hepatic uptake may have accounted for those changes. However, fasting may also affect hepatic blood flow, thereby contributing to reduced clearance of these compounds. In order to test this hypothesis, plasma clearance of antipyrine, acetaminophen and lidocaine, drugs known to be cleared by the liver yet not suspected of undergoing carrier-mediated hepatic uptake, were investigated in nine healthy adult mares (three horses/drug group) before and following a 3-day fast. Results demonstrate that fasting decreased clearance of organic anions from previous studies more than clearance of drugs used in these studies. In addition, clearance of lidocaine, the drug with the highest plasma clearance and therefore the drug most likely to be affected by reduced hepatic blood flow, was affected least by fasting. Therefore, reductions in clearance of these compounds due to fasting must not be due entirely to reductions in hepatic blood flow, but must also involve reductions in intrinsic hepatic clearance.