INHIBITORY EFFECTS OF ANTIPARASITIC DRUGS ON CYTOCHROME-P450 2D6

The interaction of antiparasitic drugs with the polymorphic cytochrome P450 2D6 was studied in human liver microsomes. Of ten different drug s tested, three quinolines, oxamniquine, primaquine and chloroquine in hibited microsomal CYP2DG-catalysed formation of l'hydroxybufuralol at concentrations that might have clinical consequences in drug use. The se drugs inhibited competitively bufuralol metabolism with K-i values of 22, 23 and 15 mu M, respectively, indicative of high affinity for t he CYP2DG-active site. The results imply that oxamniquine, primaquine and chloroquine could be substrates of cytochrome P4502 D6 or that the y are potent nonsubstrate inhibitors of the enzyme similar to quinidin e. In either case, the inhibition of CYP2D6 by these agents could lead to interference with in vivo population-phenotyping procedures in the tropical regions where treatment with the drugs is common.