Pharmacokinetics, Mass Balance, and Metabolism of [¹⁴C]TPN729, a Selective and Potent Phosphodiesterase Type 5...

TPN729 is an oral phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction. Although several studies have investigated TPN729 metabolism, quantitative data delineating the involvement of primary excretion pathways and the fraction of each metabolic pathway are limited. This study utilized radioisotope tracing methods to examine the pharmacokinetics, mass balance, and metabolism of [¹⁴C]TPN729 (100 μCi) after a single oral administration of 50 mg in healthy male Chinese participants. TPN729 was rapidly absorbed, with a time to peak concentration (T_max) of 1.58 h, suggesting that the peak plasma concentration was achieved shortly after oral administration. The elimination half-life (t_1/2) in plasma was 11.3 h, indicating that the drug was eliminated from the body at a relatively slow rate. The ratio of total drug-related chemicals in whole blood to plasma was 0.613, indicating preferential distribution in plasma. Mass balance measurements revealed that 95.7% of the radiolabeled chemical was excreted 192 h after administration predominantly through feces (78.5%) rather than urine (17.2%). This study identified 17 metabolites in plasma, urine, and feces. All metabolites were phase I metabolites and were mainly generated through dealkylation and oxidation. These findings elucidate the metabolic pathway and clearance mechanisms of TPN729 in humans.