Absorption, Tissue Distribution, Excretion, and Metabolism of 3H- and 14C-Labeled Emamectin Benzoate in Rats

Abstract

Male and female rats were administered a single high (20 mg/kg, oral) or low (0.5 mg/kg, oral or intravenous) dose of radiolabeled 4‘‘-deoxy-4‘‘-(epi-methylamino)avermectin B1a (MAB1a) benzoate. The bioavailability of MAB1a benzoate (low dose) in male and female rats was 43% and 63%, respectively. More than 98% of the total radioactivity was found in feces, with <0.4% in urine and <1.6% in the tissues. The total radioactive residues (TRR) in feces and tissues consisted of MAB1a and a single N-demethylated metabolite. The TRR contents (ppb parent equivalent) of kidney, liver, fat, muscle, spinal cord, and brain at day 1 post low oral dose in male rats were 437, 355, 241, 109, 30, and 8 ppb, respectively, and in female rats 260, 244, 192, 90, 11, and 5 ppb, respectively. The TRR contents of these tissues from both male and female rats declined to very low levels (≤12 ppb) by day 7. The TRR content of tissues at day 7 post high dose was relatively high (8−2033 ppb). Lung and spleen had higher residue contents in comparison to other tissues. Daily pretreatment with the compound for 14 days had no effect on the tissue residue levels and metabolism. Keywords: Emamectin; MK-0244; 4‘‘-deoxy-4‘‘-(epi-methylamino)avermectin B1a; 4‘‘-deoxy-4‘‘-epi-aminoavermectin B1a; residues; metabolism; HPLC