Toxicokinetics and tissue distribution of N-phenyl-phthalamic acid in male rats

To explore the absorption, tissue distribution, excretion, the change of drug blood concentrations over time and the kinetic parameters of N-phenyl-phthalamic acid (PPA) in male rats, single dose gavage was applied in the experiments. And the PPA was determined by high performance liquid chromatography. The results show that the gastrointestinal absorption was fast. In serum, the half absorption phase t1/2ka was only (0.15±0.11) h. The maximum concentration time point tmax was (0.68±0.37) h, and the peak concentration (Cmax) was (141.48±27.87) mg/L. The tissue distribution in rat was fleetly and widely. The half distribution stage t1/2α was (0.22±0.18) h, and the apparent volume of distribution Vz/F was (17.54±7.71) L/kg. The drug eliminate rapidly in vivo, and its clearance was CLz/F (1.32±0.51) (L/h)/kg. The average residence time MRT(0-∞) was (25.69±2.93) h, and the elimination half life t1/2z was (7.77±1.44) h. More than 95% of the PPA can eliminate from the body in 35 h. In this study, the bimodal phenomena was observed in the concentration-time curve of PPA. The result suggested that the cause may be the enterohepatic circulation in rats. Within 24 h, PPA could be detected in the entire tissue samples after the oral administer. The concentration order from high to low was:kidneys, lungs, liver, heart, spleen, muscle, testis, fat, and the brain. Among those, the concentration of N-phenyl-phthalamic acid in kidney reached up to 192.7 μg/g, and the targeted distribution coefficient (te) was 4.77 which was higher than 1.00. It suggested that the distribution of PPA in vivo has a relatively high selectivity to the kidney. The result of excretion study revealed that the amount of PPA existed in the feces only account for 1.45% of the overall dosage, and no PPA was detected in urine.