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• W1964038104 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 angiotensinconverting 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 ratio and 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 peptide and blunted the expected decrease in plasma atrial natriuretic peptide caused by angiotensin-converting enzyme inhibition. BMS-186716, 10 mg, did not inhibit 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. Clinical Pharmacology & Therapeutics (1999) 65, 448–459; doi:" @default.
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• W1964038104 date "1999-04-01" @default.
• W1964038104 modified "2023-10-18" @default.
• W1964038104 title "Pharmacodynamic effects of dual neutral endopeptidase–angiotensin-converting enzyme inhibition versus angiotensin-converting enzyme inhibition in humans" @default.
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• W1964038104 doi "https://doi.org/10.1016/s0009-9236(99)70140-2" @default.
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