Pharmacokinetics, distribution and excretion of PNA in rat by liquid chromatography mass spectrometry method

The pharmacokinetic profiles, tissue distribution and excretion patterns of PNA in healthy male and female Sprague-Dawley rats following a single intra-duodenum administration were investigated by previously established LC-MS method. Absorption was rapid in rats as evidenced by a short time to maximum concentration (Cmax) of 0.050 ± 0.021, 0.072 ± 0.017 and 0.067 ± 0.018 h at the 25, 50 and 100 mg/kg dose level, respectively. The Cmax were 754.9 ± 196.1, 1187.8 ± 642.1 and 2082.1 ± 1,278.5 ng/mL and the AUC0-4 were 71.8 ± 25.9, 135.2 ± 69.9 and 303.3 ± 198.3 µg/L h, which showed linear with the intra-duodenum administration range from 25-100 mg/kg. Tissues were collected at 4 time points (3, 10 min, 1 and 3 h) after dosing at 50 mg/kg. Compare to the concentrations of plasma and other tissues, the level was particularly high in the liver and brain during 3 h. Bile/urine and feces samples were collected before dosing and till 24/48 h post-dosing. The mean cumulative excretion of unchanged PNA in bile amounted to 0.021% of the dose up to 24 h. The mean recoveries of unchanged PNA were 0.0095% and 0.043% of the dose up to 48 h in urine and feces, respectively. There was no significant difference in PNA concentration observed between male and female rats during the experiments.