Pharmacodynamics and pharmacokinetics of ramipril (Hoe 498), an angiotensin converting enzyme (ACE) inhibitor, in dogs

• Published in: Japanese Journal of Pharmacology 1986, Vol.40 (suppl), p.275-275
• Main Authors: Omosu, Mikio, Yamazaki, Hiroko, Hayashi, Shoryo, Sakaguchi, Takashi
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)59570-1

Ramipril is metabolized in the body to ramipril-diacid, which shows potent antihypertensive effect. Its pharmacokinetics was studied in male beagle dogs (B.W. 10-15 kg) after ramipril administration (1 mg/kg, po, iv), and plasma hormone levels and ACE activity were also determined by RIA or HPLC. Ramipril when given orally was rapidly absorbed, and the T_max values in blood were about 10 min for ramipril and about 40 min for its diacid metabolite. The half-lives in blood were similar by both routes (ramipril, ca. 40-45 min; ramipril-diacid, ca. 65-70 min). The diacid metabolite still remained in blood (ca. 0.5 ng/ml) at 3 days after po dosing. The total amounts of ramipril and ramipril-diacid excreted in the first 48-hr urine were about 15% (po) and 40% (iv) of the administered dose, and the urinary excretion was almost completed in 3 days after po and iv treatment. The ramipril administration (po, iv) markedly increased the plasma renin activity and decreased the plasma aldosterone and angiotensin II levels from 30 min to 6 hr. The plasma ACE activity was nearly completely inhibited from 5 min to 4 hr and recovered to about 80% of the pretreatment level at 3 days. Thus, ramipril when given orally to dogs was rapidly absorbed from the intestines and remained in blood in the diacid form during a 3-day period. These results suggest that ramipril may have a prolonged duration of action.