Antipyrine and lidocaine are cleared faster in ...
|Title||Antipyrine and lidocaine are cleared faster in horses than in humans: acetaminophen may be handled similarly|
|Author(s)||L. R. Engelking, Jeanne Lofstedt, G. T. Blyden, D. J. Greenblatt|
|Abstract||The following studies were designed to evaluate plasma elimination kinetics of intravenously administered antipyrine, acetaminophen and lidocaine among 9 healthy adult horses and 9 healthy drug-free humans (3 each per drug group), in order to compare potential species differences in drug-metabolizing ability. Acetaminophen is largely biotransformed in humans by hepatic glucuronide and sulfate conjugation, whereas both antipyrine and lidocaine are oxidized by hepatic microsomal mixed-function oxidases. Thus, plasma clearances of these drugs are thought to reflect differences in hepatic oxidative and conjugative activity, and possibly hepatic blood flow in the case of lidocaine. Results showed that mean (+/- SD, n = 3) acetaminophen clearance was similar in both horses (4.84 +/- 0.637 ml/min/kg) and humans (4.68 +/- 0.691 ml/min/kg). However, antipyrine clearance was 10 times greater in horses (5.83 +/- 2.21 ml/min/kg) than in humans (0.536 +/- 0.110 ml/min/kg), which may reflect enhanced hepatic microsomal activity in horses. Although lidocaine clearance in humans was similar to estimated hepatic blood flow (20.6 +/- 5.81 ml/min/kg), clearance in horses was more than 2 times greater (52.0 +/- 11.7 ml/min/kg). The cause of the higher clearance of lidocaine in horses (like dogs) remains unexplained, and may involve significant metabolism of lidocaine at extrahepatic, extravascular sites, for intravascular degradation and renal excretion of intact lidocaine in horses was negligible. Although precise biochemical mechanisms underlying pharmacokinetic parameters for these drugs in horses were not determined, it is nonetheless concluded from antipyrine results that horses may have an enhanced ability (compared with humans) to clear drugs from the circulation that are primarily metabolized in the liver by phase I oxidative reactions.(ABSTRACT TRUNCATED AT 250 WORDS)|
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