The metabolism of avermectins B1a, H2B1a, and H2B1b by liver microsomes.
The avermectins area a new class of structurally related antiparasitic agents isolated from Streptomyces avermitilis. The major polar metabolites isolated from in vitro incubations of [3H]avermectins B1a, H2B1a, and H2B1b with either rat or steer liver microsomes have been isolated and identified as the C24-methyl alcohols of the parent compounds. A smaller quantity of a more polar metabolite has also been identified as the monosaccharide of the C24-methyl alcohols of avermectin H2H1b from rat liver microsomal incubation and avermectin H2B1a from steer liver microsomal incubation. The mass spectra and 300-MHz 1H-NMR spectra permitted assignment of structures to these metabolites. Together these two metabolites represent 50-80% of the total radioactivity more polar than the parent compounds. The metabolite profiles on reverse-phase HPLC demonstrate that the rat and steer are qualitatively similar in the production of these two polar metabolites.
D000818:Animals; D000981:Antiprotozoal Agents / Q000378:metabolism*; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D007559:Ivermectin / Q000031:analogs & derivatives; D007783:Lactones / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats
D000981:Antiprotozoal Agents; D007783:Lactones; C034045:avermectin H2B1b; C022120:avermectin B(1)a; D007559:Ivermectin; C019264:avermectin