▴ Delapril/manidipine 30mg/10mg is a new oral, once-daily, fixed combination of an ACE inhibitor and a dihydropyridine calcium-channel antagonist for the treatment of essential hypertension.
▴ In a dose-finding study in 400 patients with mild to moderate hypertension, delapril/manidipine 30mg/ 10mg once daily produced the greatest reduction in blood pressure (BP) of the combinations tested. Delapril/manidipine 30mg/10mg once daily for 6 weeks reduced systolic BP (SBP)/diastolic BP (DBP)by 15/13mm Hg.
▴ In nonresponders to monotherapy with delapril (n = 155) or manidipine (n = 152), delapril/manidipine 30mg/10mg once daily for 12 weeks reduced mean SBP/DBP by 16/11mm Hg and 16/10mm Hg, respectively.
▴ Delapril/manidipine 30mg/10mg once daily for 12 weeks in patients with mild to moderate hypertension (n = 131) demonstrated significantly greater antihypertensive efficacy than monotherapy with manidipine 10mg once daily (n = 134) or delapril 15mg twice daily (n = 136). Mean SBP/DBP reductions from baseline were 19/14, 15/11 and 14/ 10mm Hg, respectively.
▴ After 50 weeks of therapy with delapril/manidipine 30mg/10mg once daily, mean SBP/DBP was reduced by 22/14mm Hg in patients with mild to moderate hypertension (n = 309).
▴ Delapril/manidipine 30mg/10mg once daily was generally well tolerated. The incidence and nature of adverse events were similar to those observed in recipients of monotherapy with the individual agents. Combination therapy was associated with less ankle oedema than manidipine monotherapy.
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Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 Report. JAMA 2003 May 21; 289(19): 2560–72PubMedCrossRefGoogle Scholar
Guidelines Committee. 2003 European Society of Hypertension. European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21(6): 1011–53CrossRefGoogle Scholar
Guidelines Sub-Committee. 1999 World Health Organization. International Society of Hypertension guidelines for the management of hypertension. J Hypertens 1999 Feb; 17(2): 151–83Google Scholar
Gradman AH, Acevedo C. Evolving strategies for the use of combination therapy in hypertension. Current Hypertension Reports 2002; 4: 343–9PubMedCrossRefGoogle Scholar
Taylor AA, Sunthornyothin S. The case for combining angiotensin-converting enzyme inhibitors and calcium-channel blockers. Current Hypertension Reports 1999; 1: 446–53PubMedCrossRefGoogle Scholar
Razzetti R, Acerbi D. Pharmacokinetic and pharmacologic properties of delapril, a lipophilic nonsulfhydryl angiotensin-converting enzyme inhibitor. Am J Cardiol 1995 Jun 16; 75: 7–12FCrossRefGoogle Scholar
Saruta T, Nishikawa K. Characteristics of a new angiotensin converting enzyme inhibitor: delapril. Am J Hypertens 1991 Jan; 4 (1 Pt 2): 23–8SGoogle Scholar
Fogari R, Zoppi A, Mugellini A, et al. Efficacy of delapril in the treatment of mild to moderate essential hypertension: evaluation by 24-hour ambulatory blood pressure monitoring. Adv Ther 1997 Sep; 14: 254–61Google Scholar
Fogari R, Zoppi A, Corradi L, et al. Effects of different dihydropyridine calcium antagonists on plasma nore-pinephrine in essential hypertension. J Hypertens 2000; 18: 1871–5PubMedCrossRefGoogle Scholar
Mugellini A, Preti P, Zoppi A, et al. Effect of delapril-manidipine combination vs irbesartan-hydrochlorothiazide combination on fibrinolytic function in hypertensive patients with type II diabetes mellitus. J Hum Hypertens 2004 Oct; 18(10): 687–91PubMedCrossRefGoogle Scholar
Rizzoni D, Bevilacqua M, Gobbato C, et al. Blood pressure lowering effects of delapril and manidipine, in hypertensive patients with type 2 diabetes, not adequately controlled by monotherapy [abstract no. 8.6]. High Blood Press Cardiovasc Prev 2005; 12(3): 180CrossRefGoogle Scholar
Onoyama K, Nanishi F, Okuda S, et al. Pharmacokinetics of a new angiotensin I converting enzyme inhibitor (delapril) in patients with deteriorated kidney function and in normal control subjects. Clin Pharmacol Ther 1988 Mar; 43(3): 242–9PubMedCrossRefGoogle Scholar
Singlas E, Fillastre JP. Pharmacokinetics of newer drugs in patients with renal impairment (part II). Clin Pharmacokinet 1991 May; 20(5): 389–410PubMedCrossRefGoogle Scholar
Kelly JG, O’Malley K. Clinical pharmacokinetics of the newer ACE inhibitors: a review. Clin Pharmacokinet 1990 Sep; 19: 177–96PubMedCrossRefGoogle Scholar
Chiesi Farmaceutici S.p.A. Summary of product characteristics (Iperten 10mg and 20mg tablets). 2006Google Scholar
Morimoto S, Matsumura Y. Manidipine hydrochloride [CV-4093 (2HC1)]. Cardiovasc Drug Rev 1991; 9(3): 207–22CrossRefGoogle Scholar
Deroubaix X, Lins RL, Lens S, et al. Single dose pharmacokinetics of manidipine in hepatic impaired patients and healthy controls. Int J Clin Pharmacol Ther 1998; 36(7): 386–91PubMedGoogle Scholar
Stockis A, Gengler C, Goethals F, et al. Single oral dose pharmacokinetic interaction study of manidipine and delapril in healthy volunteers. Arzneimittelforschung 2003; 53(9): 627–34PubMedGoogle Scholar
Stockis A, De Bruyn S, Gengler C. Pharmacokinetics and tolerability of a new manidipine and delapril fixed oral combination in young and elderly subjects. Arzneimittelforschung 2003; 53(8): 554–61PubMedGoogle Scholar
Zoppi A, Mugellini A, Preti P, et al. Effects of the fixed combination of manidipine plus delapril in the treatment of hypertension inadequately controlled by monotherapy with either component: a phase III, multicenter, open-label, clinical trial. Curr Ther Res 2003 Jul; 64(7): 422–33CrossRefGoogle Scholar
Karpati P, Alberici M, Tocci G, et al. Long-term tolerability and efficacy of the fixed combination of manidipine and delapril in patients with essential hypertension. High Blood Press Cardiovasc Prev 2003; 10(2): 81–6CrossRefGoogle Scholar
Mugellini A, Vaccarella A, Celentano A, et al. Fixed combination of manidipine and delapril in the treatment of mild to moderate essential hypertension: evaluation by 24-hour ambulatory blood pressure monitoring. Blood Press 2005 Jul 1; 14 Suppl. 1: 6–13CrossRefGoogle Scholar
Mugellini A, Dobovisek J, Planinc D, et al. Efficacy and safety of delapril plus manidipine compared with enalapril plus hydrochlorothiazide in mild to moderate essential hypertension: results of a randomized trial. Clin Ther 2004 Sep; 26(9): 1419–26PubMedCrossRefGoogle Scholar
Bacchelli S, Degli Esposti D, Alberici M, et al. Effects of the combination of different doses of manidipine and delapril in hypertensive patients [abstract no. P-35]. Am J Hypertens 2002 Apr; 15 (4 Pt 2): 45–46ACrossRefGoogle Scholar
Ambrosioni E. Clinical evaluation of manidipine-delapril combination on efficacy and tolerability in hypertensive patients [oral presentation]. New therapeutic approach for hypertension control: the rationale for the ACE inhibitor — calcium channel blocker combination (satellite symposium of the 11 th European Meeting on Hypertension); 2001 Jun 15–19; MilanGoogle Scholar
Ambrosioni E. Manidipine and delapril in the management of hypertension. Use of a factorial design to evaluate the effects of different combinations of doses in a multicentre, controlled, randomised, double-blind clinical trial for the evaluation of the antihypertensive effect and tolerability of extemporaneous associations. (Data on file). Chiesi Farmaceutici S.p.A., 1998Google Scholar
Zannad F. Multicentre, randomised, parallel group, double-blind, double-dummy, phase III study to compare the antihypertensive effects and tolerability of delapril and manidipine monotherapy to delapril plus manidipine (CHF 1521 fixed combination) in patients with mild to moderate essential hypertension. (Data on file). Chiesi Farmaceutici S.p.A., 2004Google Scholar
Chiesi Farmaceutici S.p.A. Summary of product characteristics (Delaket 15mg and 30mg tablets). 2005Google Scholar
Fogari R, Malamani G, Derosa G, et al. Effect of delapril addition to manidipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients [abstract no. P-205]. Am J Hypertens 2003 May; 16 (5 Pt 2): 113ACrossRefGoogle Scholar