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 antagonis t that acts as a specific inhibitor of the renin-angiotensin system. I n this study, 36 healthy male volunteers were administered single and repeated oral doses of TCV-116 to investigate its effects on blood pre ssure and heart rate, and to evaluate the safety and pharmacokinetics of the drug. At single doses of 2.5 mg and greater, TCV-116 significan tly lowered blood pressure even in normotensive subjects. This hypoten sive effect was maintained during repeated administration on a once-da ily regimen over an 8-day period. Serum concentration of M-1, an activ e metabolite of TCV-116, increased in a dose-dependent manner, reachin g a peak 3 to 4 hours after administration. An amount of M-1 equivalen t to approximately 10% of the administered dose of TCV-116 was excrete d in the urine during the first 24 hours following administration. No accumulation of M-1 was observed in subjects receiving repeated admini stration of TCV-116. No adverse effects were observed except for mild headache in three subjects. These results suggest that the renin-angio tensin system plays a role in the regulation of blood pressure, even i n normotensive subjects, and that TCV-116 may prove to be useful in th e treatment of hypertension.