Pharmacokinetics, pharmacodynamics, and safety interaction study of tunodafil hydrochloride and alcohol: A randomized, blinded, placebo-controlled, three-cycle crossover study in Chinese healthy men.

OBJECTIVES

This study aimed to evaluate the pharmacodynamic effects of administering tunodafil hydrochloride with alcohol on blood pressure and heart rate in healthy Chinese males, and to investigate the mutual pharmacokinetic interactions and safety of the combination.

METHODS

The trial was a randomized, blinded, placebo-controlled, three-cycle crossover design, with one administration in each cycle and a 7-day washout interval between cycles. Eighteen healthy men were randomized to receive tunodafil hydrochloride with an alcoholic beverage, placebo with an alcoholic beverage, or tunodafil hydrochloride with a placebo beverage in each cycle. The primary endpoints included plasma concentrations of tunodafil, metabolite M459, and alcohol, as well as supine blood pressure and heart rate measurements. The secondary endpoint was the incidence of adverse events.

RESULTS

Pharmacokinetic results demonstrated that the combined drug and alcohol group did not affect plasma alcohol concentration compared to alcohol alone. However, co-administration led to increased systemic exposure of tunodafil and its metabolite M459: AUC0-∞ rose by 42.89% and 28.75%, while Cmax increased by 74.46% and 39.32%, respectively, compared to the drug alone group. Pharmacodynamic analysis indicated that the reduction in blood pressure was primarily driven by alcohol consumption, with no significant additional effect from tunodafil co-administration. In contrast, heart rate elevation was notably amplified when both drug and alcohol were given together, exceeding the effects of either substance alone. Safety results reported 149 grade-one adverse events.

CONCLUSION

The study concluded that tunodafil hydrochloride, when taken with alcohol, does not interfere with alcohol metabolism but moderately enhances the tunodafil and metabolite exposure. Alcohol remained the dominant factor in lowering blood pressure, while tunodafil contributed to an additive increase in heart rate. The combination does not significantly increase adverse events.