Incidence of a subclinical fascioliasis on antipyrine clearance and metabolite excretion in sheep.
1. The pharmacokinetics of i.v. antipyrine (25 mg/kg) used as a model compound, were determined in young male sheep, before and each month after an oral infestation by 150 metacercariae of Fasciola hepatica, and 8 weeks following a flukicidal treatment. 2. The parasitic pathology was ascertained by the clinical observation of animals and the increase in plasma antibodies directed against liver flukes. 3. A significant decrease in the total plasma clearance of the drug occurred by week 4 to 16, and a 1.7 fold increase in mean residence time occurred by week 12 post-infection. 4. Urinary excretion of antipyrine metabolites was determined before and 8 weeks following the infestation. 4-Hydroxyantipyrine was the major urinary metabolite and its excretion was decreased by 30% in infected sheep, whereas there was no change in the excretion of norantipyrine, 3-hydroxymethylantipyrine or unmetabolized drug. 5. It is concluded that the impairment of antipyrine clearance in the course of fascioliasis could be related to the decrease in liver microsomal cytochrome P-450-dependent mono-oxygenases observed in sheep with a similar parasitic burden.
Tufenkji
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AE
Laboratoire de Pharmacologie-Toxicologie, INRA, Toulouse, France.
Alvinerie
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M
Pineau
T
T
Boulard
C
C
Galtier
P
P
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D003577:Cytochrome P-450 Enzyme System; D005211:Fascioliasis / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D008657:Metabolic Clearance Rate; D010105:Oxygenases / Q000378:metabolism; D012756:Sheep
C007983:4-hydroxyantipyrine; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D000983:Antipyrine