Possible isozyme-specific effects of experimental malaria infection with Plasmodium berghei on cytochrome P450 activity in rat liver microsomes.
We have investigated the effect of experimental malaria infection on rat cytochrome P450-mediated drug metabolism using ethoxyresorufin and metoprolol as probe compounds. Malaria infection caused a significant reduction in total intrinsic clearance of ethoxyresorufin in both low and high parasitaemia malaria compared with control (control 18.7 +/- 7.2; low parasitaemia 10.5 +/- 4.1; high parasitaemia 4.3 +/- 1.4 mL min-1). However, clearance of metoprolol was unchanged in malaria infection compared with control (control 2.7 +/- 1.2; malaria 4.0 +/- 1.7 mL min-1). The change in clearance of ethoxyresorufin was the result of a decrease in Vmax, with no apparent change in Km. There was no change in either Vmax or Km of metoprolol. These results indicate a possible isozyme-selective effect of experimental malaria.
Glazier
A P
AP
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
Kokwaro
G O
GO
Edwards
G
G
D000107:Acetylation; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004195:Disease Models, Animal; D007527:Isoenzymes / Q000378:metabolism*; D008288:Malaria / Q000188:drug therapy / Q000201:enzymology*; D008297:Male; D008790:Metoprolol / Q000378:metabolism / Q000627:therapeutic use; D008862:Microsomes, Liver / Q000201:enzymology*; D010078:Oxazines / Q000378:metabolism / Q000627:therapeutic use; D010962:Plasmodium berghei; D051381:Rats; D017208:Rats, Wistar
D007527:Isoenzymes; D010078:Oxazines; C007649:ethoxyresorufin; D003577:Cytochrome P-450 Enzyme System; D008790:Metoprolol