The effect of malaria infection on paracetamol disposition in the rat.
The effect of Plasmodium berghei infection, a rodent malarial model, on the disposition of paracetamol (50 mg/kg, i.v.) was investigated in rats. Malaria infection (MI) resulted in a significant decrease in clearance (control: 21.6 +/- 5.5 vs test: 11.8 +/- 2.9 mL/min/kg, P less than 0.005) with no change in volume of distribution and a significant prolongation of the elimination half-life (control: 30.7 +/- 6.3 vs 53.3 +/- 12.1 min, P less than 0.005) of paracetamol in malaria infected rats. These changes were not related to the severity of MI. Malaria infection also decreased biliary clearance of paracetamol (64%) but not its glucuronide and sulphate conjugates in the bile compared with controls. In addition, glutathione conjugates were not detected in bile samples of malaria infected rats. These data suggest that important pathways of drug detoxification may be compromised by MI in a relatively selective fashion and the relevance of these findings to the clinical use of drugs eliminated by these pathways merits further study.
Mansor
S M
SM
Department of Pharmacology and Therapeutics, University of Liverpool, U.K.
Edwards
G
G
Roberts
P J
PJ
Ward
S A
SA
D000082:Acetaminophen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D001646:Bile / Q000378:metabolism; D006207:Half-Life; D008658:Inactivation, Metabolic; D008099:Liver / Q000378:metabolism*; D008288:Malaria / Q000378:metabolism*; D008297:Male; D051379:Mice; D051381:Rats
D000082:Acetaminophen; C037386:acetaminophen glucuronide; C045667:acetaminophen sulfate ester