Pharmacokinetics and Safety of TPN171 (a PDE5 Inhibitor) in Patients With Mild or Moderate Hepatic Impairment Versus Participants With Normal Hepatic Function: A Phase 1 Study.

TPN171 is a phosphodiesterase-5 inhibitor. It is currently being developed in China to treat pulmonary arterial hypertension and erectile dysfunction (ED). This study aimed to compare the pharmacokinetics and safety of TPN171 across participants with normal hepatic function and hepatic impairment (HI). An open-label, single-dose, parallel-group study enrolled participants with normal hepatic function (group C) and mild-to-moderate HI (groups A and B). In each cohort, 8 participants completed the study. Blood samples were collected up to 72 hours after 10 mg oral TPN171 administration. The maximum plasma concentration (Cmax), area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC0-t), and AUC extrapolated to infinite time (AUC0-∞) were compared between the groups. Cmax, AUC0-t, and AUC0-∞ were higher in groups A and B than in group C (geometric mean ratios 1.17-1.20, 1.46-1.53, and 1.45-1.54, respectively), while the elimination half-time was prolonged and clearance was reduced in the HI groups. All adverse events were not serious and no participant withdrew from this study. Considering the increase in TPN171 plasma exposure, the highest dose of 5 mg TPN171 is recommended in patients with ED having mild-to-moderate HI.