TOXICOLOGICAL EVALUATION OF PIDOTIMOD

This paper reports the toxicological evaluation of pidotimod ((R)-3-[( S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PG T/1A, CAS 121808-62-6). Its acute toxicity in mice, rats and dogs was very low after oral, i.v., i.m. and i.p. administration. The repeated administration studies in rats were performed for 4 months via the i.p . route and for 12 months via the oral route. Pidotimod did not show t oxic effects at dosages up to 200 mg/kg i.p. and 800 mg/kg p.o. These dosages correspond to 32.5 times the maximum dosage intended for clini cal use. The repeated administration studies in dogs were performed fo r 26 creeks via the i.m. route and for 52 weeks via the oral route. Pi dotimod did not show toxic effects at dosages up to 300 mg/kg i.m. and 600 mg/kg p.o.. It did not affect male or female rat fertility at dos ages up to 600 mg/kg by oral and 500 mg/ kg by i.v. route. The compoun d was not teratogenic in rats (600 mg/kg p.o. and 1000 mg/kg i.v.), wi th no effects on subsequent embryofoetal development at dosages up to 1000 mg/kg/day, and in rabbits (300 mg/kg p.o. and 500 mg/kg. i.v.). T here were no peri- and post-natal toxic effects in rats (600 mg/kg p.o . and 500 mg/kg i.v.). Local tolerability of pidotimod after i.m. admi nistration was very good. In conclusion pidotimod is chracterized by a high safety margin in all animal species.