Clinical pharmacodynamic studies with cilazapril and a combination of cilazapril and propranolol.

We evaluated the degree of inhibition of angiotensin converting enzyme (ACE), principally by cilazapril, by assessing the blood pressure response to a continuous infusion of increasing doses of angiotensin I, and assessed the possible pharmacokinetic and pharmacodynamic interactions between cilazapril and propranolol in healthy volunteers and patients with mild to severe essential hypertension. The specificity of the angiotensin I infusion method was verified when a single dose of cilazapril 30mg antagonised the increase in diastolic blood pressure induced by angiotensin I but did not influence the response to angiotensin II. Using this method, we showed that single oral doses of cilazapril 4 mg, captopril 25 mg and enalapril 10mg shifted the angiotensin I dose-effect curve to the right and determined a pharmacological half-life of about 4 hours for cilazapril. Increasing single oral doses (1.25, 3.75, 10 and 30mg) of cilazapril reduced diastolic blood pressure dose-dependently and shifted the angiotensin I dose-response curves to the right. The dose representing 50% inhibition of ACE activity (apparent Ki-dose) was about 0.6mg, 3 hours after cilazapril administration. Cilazapril and propranolol did not exhibit any clinically significant pharmacokinetic interaction in healthy volunteers; each drug reduced diastolic and systolic blood pressure by about 7 mm Hg, and this was doubled by the combination. Cilazapril had no significant effect on heart rate, in patients with essential hypertension whereas both propranolol and the combination of cilazapril and propranolol reduced it. Monotherapy with each drug reduced blood pressure, and combined administration enhanced the antihypertensive effect.(ABSTRACT TRUNCATED AT 250 WORDS)

RCT Entities:   Population Interventions Outcomes