1979 Volume 14 Issue 2 Pages 79-91
The pharmacokinetic and toxicological examinations of piromidic acid (PA, 8-ethyl-5, 8-dihydro-5-oxo-2-pyrrolidinopyrido[2, 3-d]pyrimidine-6-carboxylic acid) were studied in ayu Plecoglossus altivelis, amago salmon Oncorhynchus rhodurus and eels Anguilla japonica and A. anguilla orally administered a single or multiple dose(s) of PA with the following results.
1. The absorption, distribution and excretion data obtained from the bioassay revealed that orally administered PA was easily absorbed and quickly became distributed in blood and major organs. Peak levels were reached in 3 h (in ayu) or 6-24 h (in amago salmon) after the administration of PA, followed by a gradual decrease. The levels of PA in liver and kidney were higher than in blood and plasma.
2. In acute toxicity study, the LD50 value for ayu was more than 2, 000 mg/kg. The subacute toxicity of PA was studied in ayu (80 mg/kg), amago salmon (800 mg/kg) and eels (400 mg/kg) administered PA once daily for 5-10 days. Except for accidental death of two eels, all fishes receiving PA survived without any clinical and histopathological changes.
3. Disappearance of PA from the tissues in amago salmon was studied after the administration of 40 mg/kg of PA for 7 consecutive days. Peak levels of PA in the tissues tested attained within 6-12 h following administration. A level below the assay limits (0.25-0.56 μg/ml or g) was reached 96 h post dosing. No evidence of long term residue was found in any of the tissues tested.
