Pharmacokinetic and pharmacodynamic interactions between the ACE inhibitor cilazapril and beta‐adrenoceptor antagonist propranolol in healthy subjects and in hypertensive patients.

Abstract

1 Six healthy subjects received cilazapril (2.5 mg once daily), propranolol (120 mg once daily), the combination of both and placebo for a period of 1 week each (wash-out phase 1 week). 2 Propranolol and cilazapril reduced systolic and diastolic blood pressure (BP) by 7 mm Hg at peak when compared with placebo. However after the combination, this reduction was more than doubled (18 mm Hg) and lasted longer. 3 There was a trend to lower and later peak concentrations for both drugs after administration of the combination. No clinically relevant pharmacokinetic interactions between cilazapril and propranolol were found. 4 The effects on blood pressure were confirmed in hypertensive patients (BPdiastolic > 95 mm Hg). Thirteen patients were randomly allocated cilazapril (2.5 mg day'-) or propranolol (120 mg day-1)) as part of a cross-over design. This was then followed by the combination. All treatment periods were of 3 weeks duration and all measurements were done 2 h after drug administration. 5 Cilazapril lowered the median sitting diastolic BP by 8 mm Hg, and propranolol by 9 mm Hg, whereas the combination reduced the diastolic BP by 19 mm Hg.6 The results of these studies, attempting to elucidate drug-drug interactions, showed that combined use of propranolol and cilazapril resulted in a more pronounced and longer lasting blood pressure reduction, in healthy subjects and in patients with hypertension.

Effects on Plasma Angiotensin‐Converting Enzyme Activity and Circulating Renin of Lisinopril and Enalapril Alone and in Combination with Propranolol in Healthy Volunteers

“…These findings are consistent with results obtained with other angiotensin-converting enzyme inhibitors as captopril and propranolol (MacGregor et al 1982), ramipril andpropranolol (van Griensven et al 1993), and cilazapril and propranolol (Belz et a/. 1989b), showing adrenergically mediated release of renin.…”

“…This study showed that the addition of a P-adrenergic blocking agent blunted the increase in plasma renin activity induced by angiotensin-converting enzyme inhibitors, in the 24 hr study period in healthy subjects. These findings are consistent with results obtained with other angiotensin-converting enzyme inhibitors as captopril and propranolol (MacGregor et al 1982), ramipril andpropranolol (van Griensven et al 1993), and cilazapril and propranolol (Belz et a/. 1989b), showing adrenergically mediated release of renin.…”

Effectively targetting the renin-angiotensin-aldosterone system in cardiovascular and renal disease: rationale for using angiotensin II receptor blockers in combination with angiotensin-converting enzyme inhibitors

“…[130][131] When combining β-blockers and ACE-I in therapy, study results have been mixed, as some studies have demonstrated an additive antihypertensive effect while others showed no additive effect. [131][132][133][134][135][136][137][138][139][140][141][142][143][144] The mechanism for the added hypotensive effect may be unrelated to dual effects on the RAAS, since non-RAAS related antihypertensive effects of β-blockade may be involved. 145 However, the additive antihypertensive effect of combining ACE-I and β-blockers is small and is clinically insignificant.…”