Tissue residues of arprinocid in chickens. 1. Depletion of residues in tissues of chickens fed carbon-14-labeled arprinocid

Abstract

Chickens were fed diets containing 60-80 ppm of the anticoccidial agent arprinocid starting at 3-9 days of age and ending at 49-60 days of age. In these experiments the chickens were fed 14C-labeled drug during the last 4 or 14 days or the total 44 days of the dosing. Of the edible tissues, liver retained the largest radioactive residue after withdrawal of drug from the diet These residues consisted of two pools, a rapidly depleting pool and a persistent, slowly depleting pool. The persistent pool represents about 15% of the total residue at drug withdrawal and about 100% of the residue 5 days after drag withdrawal. The results of the 4-day pulse were used to estimate the steady-state level of residues due to the persistent pool. The estimated value was in good agreement with that found on lifetime exposure to radioactive drug.Arprinocid [MK-302; 9-[(2-chloro-6-fluorophenyl)methyl]-9H-imrin-6-amine; I] is of interest for control of i Arprinocid coccidiosis in broiler chickens (Kilgore et al., 1978; Miller et al., 1977;Olson et al., 1978;Tamas et al., 1978). Tissue distribution studies with the 14C-labeled compound showed that of the edible tissues liver contained the largest radioactive residue. At 3-5 days after drug withdrawal, radioactivity was equivalent to about 0.1-0.3 ppm, expressed as arprinocid (Olson et al., 1976).In actual use arprinocid would be administered daily in poultry feed at levels of 0.006% (60 ppm). To design a meaningful tissue residue experiment with radioactive drug, one must establish the length of the period of dosing with nonradioactive drug and the length of the period for dosing with radioactive drug. In a series of five experiments, the dosing with nonradioactive drug was followed by a 4or 14-day pulse of labeled drug. In a sixth experiment, only radioactive drug was administered for 44 days. The effect of the dose level, duration of the radioactive pulse, and the withdrawal period on the tissue residue was noted. MATERIALS AND METHODSArprinocid. Arprinocid, obtained from the Merck Sharp & Dohme Research Laboratories sample collection, was synthesized by reaction of 2-chloro-6-fluorobenzyl chloride with adenine. The product was greater than 98% in purity and contained about 1.0-1.2% of the 3-substituted adenine. (The commercial product contains less than 0.005% of the 3 isomer.) Animal Handling. Sex-separated Hubbard-Hubbard chickens were weighed and sorted into groups for each experiment. The experiments were usually initiated with