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THE ACUTE HEMODYNAMIC, HORMONAL, AND PHARMACOKINETIC PROPERTIES OF ORAL SPIRAPRIL IN PATIENTS WITH MODERATE TO SEVERE HEART-FAILURE

VANDENBROEK, SAJ., VANBRUGGEN, A., DEGRAEFF, PA., HILLEGE, H., VANGILST, WH., WESSELING, H. & LIE, KI., Oct-1991, In : Journal of Cardiovascular Pharmacology. 18, 4, p. 614-621 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

The acute hemodynamic, hormonal, and pharmacokinetic responses to the oral angiotensin-converting enzyme (ACE) inhibitor spirapril were studied in 15 patients with moderate to serve congestive heart failure in a baseline controlled dose-ranging study. Doses of 0.3, 1.0, 1.5, 3.125, and 6.25 mg were investigated for 24 h in three groups of five patients each. All doses demonstrated a significant reduction in serum ACE, even after 24 h. Significant reductions in mean arterial pressure, systemic vascular resistance, and pulmonary capillary wedge pressure were observed with doses > 1.0 mg spirapril. Maximal significant hemodynamic effects occurred approximately 4-6 h after drug administration. The plasma concentrations of spirapril and its metabolite spiraprilate were dose-dependent. After administration of spirapril, the quick rise to the peak level of spiraprilate suggests rapid metabolism of spirapril into spiraprilate and a slow elimination of this metabolite. No severe hypotension or other serious side effects occurred in the patients studied. The results indicate that spirapril may be expected to be an effective drug in the treatment of congestive heart failure. From our findings we conclude that 1.5 mg spirapril is an optimal starting dose in patients with moderate to severe congestive heart failure.

Original languageEnglish
Pages (from-to)614-621
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume18
Issue number4
Publication statusPublished - Oct-1991

    Keywords

  • SPIRAPRIL, CONGESTIVE HEART FAILURE, ANGIOTENSIN-CONVERTING ENZYME INHIBITOR, ANGIOTENSIN-CONVERTING ENZYME, INHIBITORS ENALAPRIL, HEALTHY-SUBJECTS, CAPTOPRIL, PHARMACODYNAMICS, LISINOPRIL, PLASMA, SYSTEM, AGE

ID: 6296754