Abstract
The pharmacokinetic studies of piromidic acid (PA, 5, 8-dihydro-8-ethyl-5-oxo-2-pyrrolidinopyrido [2, 3-d] pyrimidine-6-carboxylic acid=2-pyrrolidino-PPA) were performed in human subjects after oral administration. A compartment model involved thirteen parameters was adopted, in which PA compartment was connected to each compartment in branched metabolic pathway. Each parameter was determined by mathematical method, and a trial and error procedure using the experimental data on blood levels and urinary excretion in man receiving oral PA. Calculated urinary excretion of PA or its metabolites was found to be reasonable. Combined amounts calculated for biological active materials, PA, M-II (2-(2-hydroxypyrrolidino)-PPA) and M-V (2-(3-hydroxypyrrolidino)-PPA) were found to be in good agreement with those by bioassay, demonstrating that this pharmacokinetic model is valid to lead to better understanding of chemotherapeutic effect of PA.
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