Abstract
This study aimed to evaluate the effects of the concomitant administration of TPN171 and alcohol on hemodynamic and pharmacokinetic characteristics in healthy Chinese male subjects. Fifteen eligible subjects were randomly assigned to one of three sequences, each comprising three treatments: Treatment A (placebo +0.5 g/kg alcohol), Treatment B (TPN171 + 0.5 g/kg alcohol), and Treatment C (TPN171 + placebo). Enrolled subjects were administered with 10 mg TPN171 and/or 0.5 g/kg alcohol in fasting state in a randomized crossover design. Blood pressure, pulse rate (PR), blood samples, and breath alcohol test were measured at designated time points for hemodynamic and pharmacokinetic analyses. Compared with 10 mg TPN171 alone, administration of 10 mg TPN171 + 0.5 g/kg alcohol significantly lowered the area under the effect-time curve from 0 to 4 h (AUEC(0-4h)) of systolic blood pressure (95% confidence interval [CI]: -29.75 to -0.83, p = 0.039) and significantly increased AUEC(0-4h) of PR (95% CI: 7.47-28.92, p = 0.003). Compared with 0.5 g/kg alcohol alone, administration of 10 mg TPN171 + 0.5 g/kg alcohol contributed to significantly higher maximal increase of PR (95% CI: 2.78-9.44, p = 0.002) and AUEC(0-4h) of PR (95% CI: 1.08-24.52, p = 0.035). Alcohol had no influence on the pharmacokinetics of TPN171, and vice versa. Though the concomitant administration of TPN171 and alcohol induced a more pronounced increase in PR, this did not result in clinical symptoms or heart rate increase-related adverse events, indicating that the combined use was generally safe and well-tolerated.