Selective effects of a bacterial infection (Actinobacillus pleuropneumoniae) on the hepatic clearances of caffeine, antipyrine, paracetamol, and indocyanine green in the pig.
1. In order to investigate the effect of a bacterial acute phase response model on drug disposition in vivo, plasma clearances of antipyrine, caffeine, paracetamol and indocyanine green were investigated in the healthy and Actinobacillus pleuropneumoniae-infected pig. 2. Indocyanine green plasma and endogenous creatinine clearance were not changed during the infection, which indicates that hepatic blood flow and renal function were not significantly affected. 3. In the A. pleuropneumoniae-infected pig, plasma clearances of antipyrine and caffeine, both marker substrates for hepatic oxidative biotransformation, were decreased by 72 and 68% respectively. The clearance of paracetamol, a drug mainly glucuronidated in the pig, was reduced by 39%. 4. It is concluded that the most important change in drug elimination during an acute phase response induced by A. pleuropneumoniae is a suppression of oxidative hepatic biotransformation.
Monshouwer
M
M
Department of Veterinary Basic Sciences, University of Utrecht, The Netherlands.
Witkamp
R F
RF
Nijmeijer
S M
SM
Pijpers
A
A
Verheijden
J H
JH
Van Miert
A S
AS
D000082:Acetaminophen / Q000493:pharmacokinetics; D000189:Actinobacillus Infections / Q000378:metabolism*; D016977:Actinobacillus pleuropneumoniae; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D002110:Caffeine / Q000493:pharmacokinetics; D003404:Creatinine / Q000097:blood / Q000652:urine; D007208:Indocyanine Green / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D013552:Swine
C007983:4-hydroxyantipyrine; D000082:Acetaminophen; D002110:Caffeine; D003404:Creatinine; D007208:Indocyanine Green; D000983:Antipyrine