KEY RESULTS
Thirteen different metabolites (M1-M13) were identified after incubation
of ivermectin with human liver microsomes. Three (M1, M3, and M6) were
the dominant metabolites found in microsomes, hepatocytes, and blood
from volunteers after oral ivermectin administration. The chemical
structure defined by LC-MS/MS and NMR indicated that M1 is
3″-O -demethyl ivermectin, M3 is 4-hydroxymethyl ivermectin, and
M6 is 3″-O -demethyl, 4-hydroxymethyl ivermectin. Metabolic
pathway evaluations with characterized cytochrome P450 enzymes showed
that M1 was produced by CYP3A4 and CYP3A5, and that M3 and M6 were
produced by CYP3A4.