Pharmacokinetic-pharmacodynamic model relating spiraprilat plasma concentrations to systemic and regional hemodynamic effects in congestive heart failure.
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| Abstract |
The aim of this study was to investigate the relations between the plasma concentrations of spiraprilat (the active metabolite of the angiotensin-converting enzyme inhibitor spirapril) and its effects on plasma converting enzyme activity (PCEA), pulmonary capillary wedge pressure (PCWP), and brachial blood flow (BBF), after a single oral administration of 6 mg of spirapril in eight patients with severe congestive heart failure (CHF). Concentrations and effects were determined before and repeatedly during 48 h after drug intake. A sigmoid model was fitted to individual observations. Maximal effects, concentrations inducing half-maximal effects, and Hill coefficients were -99 +/- 2%, 3.9 +/- 1.9 ng/ml, and 2.4 +/- 0.7 for PCEA inhibition, -15 +/- 8 mm Hg, 11.8 +/- 9.2 ng/ml, and 2.6 +/- 1.3 for PCWP decrease, and 36 +/- 19 ml/min, 13.8 +/- 7.6 ng/ml, and 3.3 +/- 1.0 for BBF increase. In severe CHF, although a 14 ng/ml plasma concentration of spiraprilat may induce a 95% inhibition of PCEA, a 30 ng/ml plasma concentration is mandatory to normalize PCWP and BBF. This concentration corresponds to the peak achieved after a 6-mg oral dose of spirapril.
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| Authors | E Bellissant, N P Chau, C Thuillez, C Gerbeau, C Richard, J F Giudicelli |
| Journal | Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 30 Issue 2 Pg. 253-60 (Aug 1997) ISSN: 0160-2446 [Print] United States |
| PMID | 9269955 (Publication Type: Clinical Trial, Journal Article) |
| Chemical References |
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