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 V(max), with no apparent change in K(m). There was no change in either V(max) or K(m) of metoprolol. These results indicate a possible isozyme-selective effect of experimental malaria.