Effects of the angiotensin II receptor antagonist, TCV-116, on blood pressure and the renin-angiotensin system in healthy subjects.

TCV-116 is a new, nonpeptide, angiotensin II type-1 receptor antagonist that acts as a specific inhibitor of the renin-angiotensin system. In this study, 36 healthy male volunteers were administered single and repeated oral doses of TCV-116 to investigate its effects on blood pressure and heart rate, and to evaluate the safety and pharmacokinetics of the drug. At single doses of 2.5 mg and greater, TCV-116 significantly lowered blood pressure even in normotensive subjects. This hypotensive effect was maintained during repeated administration on a once-daily regimen over an 8-day period. Serum concentration of M-1, an active metabolite of TCV-116, increased in a dose-dependent manner, reaching a peak 3 to 4 hours after administration. An amount of M-1 equivalent to approximately 10% of the administered dose of TCV-116 was excreted in the urine during the first 24 hours following administration. No accumulation of M-1 was observed in subjects receiving repeated administration of TCV-116. No adverse effects were observed except for mild headache in three subjects. These results suggest that the renin-angiotensin system plays a role in the regulation of blood pressure, even in normotensive subjects, and that TCV-116 may prove to be useful in the treatment of hypertension.