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Titolo:
Pharmacodynamic effects of dual neutral endopeptidase-angiotensin-converting enzyme inhibition versus angiotensin-converting enzyme inhibition in humans
Autore:
Massien, C; Azizi, M; Guyene, TT; Vesterqvist, O; Mangold, B; Menard, J;
Indirizzi:
Hop Broussais, Clin Invest Ctr 9201, INSERM, F-75674 Paris 14, France Hop Broussais Paris France 14 Ctr 9201, INSERM, F-75674 Paris 14, France Assistance Publ Hop Paris, Paris, France Assistance Publ Hop Paris ParisFrance ce Publ Hop Paris, Paris, France Bristol Myers Squibb Pharmaceut Res Inst, Princeton, NJ 08543 USA Bristol Myers Squibb Pharmaceut Res Inst Princeton NJ USA 08543 08543 USA
Titolo Testata:
CLINICAL PHARMACOLOGY & THERAPEUTICS
fascicolo: 4, volume: 65, anno: 1999,
pagine: 448 - 459
SICI:
0009-9236(199904)65:4<448:PEODNE>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
ATRIAL-NATRIURETIC-PEPTIDE; ESSENTIAL-HYPERTENSION; BLOOD-PRESSURE; HEART-FAILURE; MYOCARDIAL-INFARCTION; HORMONAL RESPONSES; MIXED INHIBITOR; RENAL-FUNCTION; RENIN RELEASE; HEALTHY-MEN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
61
Recensione:
Indirizzi per estratti:
Indirizzo: Azizi, M Hop,Broussais, Clin Invest Ctr 9201, INSERM, 96 Rue Didot, F-75674 Paris 14 Hop Broussais 96 Rue Didot Paris France 14 dot, F-75674 Paris 14
Citazione:
C. Massien et al., "Pharmacodynamic effects of dual neutral endopeptidase-angiotensin-converting enzyme inhibition versus angiotensin-converting enzyme inhibition in humans", CLIN PHARM, 65(4), 1999, pp. 448-459

Abstract

Background: There is currently no clear evidence that dual neutral endopeptidase-angiotensin-converting enzyme inhibitors have effects on angiotensin-converting enzyme, renin, or blood pressure that are different from specific angiotensin-converting enzyme inhibitors in humans. Methods and results In a double-blind, placebo-controlled crossover study single oral doses of the dual neutral endopeptidase-angiotensin-converting enzyme inhibitor, 10 mg BMS-186716 and the angiotensin-converting enzyme inhibitor fosinopril (20 mg) were administered to 9 normotensive subjects with induced mild sodium depletion. Values for area under the time curve from 0 to 24 hours [AUC(0-24)] for the plasma angiotensin II/angiotensin I ratioand for angiotensin II were similar for 10 mg BMS-186716 and 20 mg fosinopril, Plasma atrial natriuretic peptide decreased significantly after 20 mg fosinopril (9 +/- 3 pg/mL; P < .05 versus 10 mg BMS-186716 and placebo) compared with 10 mg BMS-186716 (16 +/- 5 pg/mL) and placebo (16 +/- 5 pg/mL), BMS-186716, 10 mg, significantly increased urinary atrial natriuretic peptide from baseline by 2 +/- 1.3-fold (P < .05 versus placebo and 20 mg fosinopril). AUC(0-24) of plasma active renin did not differ significantly between 10 mg BMS-186716 (3898 +/- 333 pg.h.mL(-1)) and 20 mg fosinopril (4383 +/- 302 pg.h.mL(-1); difference not significant). Both drugs decreased blood pressure, but the AUC(0-24) of the changes in mean blood pressure differed significantly from placebo (79 +/- 84 mm Hg.h) only for 20 mg fosinopril (181 +/- 6 mm Hg.h; P < .05) but not for 10 mg BMS-186716 (118 +/- 7 mmHg.h),Conclusions: In this model, single oral doses of 10 mg BMS-186716 and 20 mg fosinopril induced similar 24-hour in vivo angiotensin-converting enzyme inhibition. BMS-186716, 10 mg, increased urinary atrial natriuretic peptideand blunted the expected decrease in plasma atrial natriuretic peptide caused by angiotensin-converting enzyme inhibition. BMS-186716, 10 mg, did notinhibit plasma active renin rise compared with 20 mg fosinopril, A single oral dose of 10 mg BMS-186716 had a shorter blood pressure-lowering effect than 20 mg fosinopril.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 13:35:53