Pharmacokinetics of pidotimod in rats and dogs.
The pharmacokinetic studies on pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) a new biological response modifier, following intravenous, intramuscular or oral administrations in rats and dogs are reported in this paper. Plasma, urine and organ concentrations were determined by HPLC. Analytical methods were validated for specificity, sensitivity, recovery, accuracy and reproducibility; recovery was very close to 100%, the coefficients of variation of accuracy and reproducibility showed low values. In the rat the pharmacokinetic parameters obtained after oral administration demonstrate that pidotimod is a very fast absorbed, distributed and eliminated drug (t1/2el = 1 h) and that it shows high total clearance and distribution volume. Bioavailability was 100% in the intramuscular route and 27% in the oral route. Pidotimod distributes quickly in the main organs, in particular in kidneys and liver; the time course of the levels in organs follows that of plasma levels after intramuscular administration. After repeated intramuscular administrations no phenomena of accumulation or autoinduction were evident. The urinary excretion of the unmodified drug is 75.6% after intravenous and 31.1% after oral administration. The behaviour of pidotimod in dog after oral administration is quite similar to that observed in rat, with a t1/2el of 1.47 h, absolute bioavailability of 37%, high total clearance and distribution volume. Also in the dog the repeated intravenous and oral administrations do not cause any accumulation or autoinduction phenomena.
Coppi
G
G
Research Centre, Poli Industria Chimica S.p.A., Milan, Italy.
Silingardi
S
S
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006207:Half-Life; D007155:Immunologic Factors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D053778:Thiazolidines; D014018:Tissue Distribution
D007155:Immunologic Factors; D013844:Thiazoles; D053778:Thiazolidines; C064893:pidotimod; D011761:Pyrrolidonecarboxylic Acid