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Chemical Compound Review:

SPIRAPRILAT (7S)-8-[(2S)-2-[[(1S)-1- carboxy-3-phenyl...

Synonyms: Spiraprilate, Spiraprilatum, CHEMBL579, SCH-33861, CHEBI:116952, ...

Krähenbühl, S. et al., Gérard, J.L. et al., Meredith, P.A. et al., Noble, S. et al., Bellissant, E. et al., et al.

Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Sch 33861

Spirapril is a non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor prodrug which is converted to the active metabolite spiraprilat following oral administration, and which has been evaluated primarily for the treatment of hypertension [1].
Pharmacokinetic-pharmacodynamic model relating spiraprilat plasma concentrations to systemic and regional hemodynamic effects in congestive heart failure [2].
In contrast, the bioavailability of spiraprilat, the metabolite responsible for the pharmacological action of spirapril, was significantly reduced in patients (AUC 820 micrograms.h.l-1, 923 micrograms.h.l-1 and 1300 micrograms.h.l-1 in patients with cirrhosis, patients with non-cirrhotic liver disease and in healthy subjects, respectively [3].
Pharmacokinetics of spirapril and spiraprilat in patients with chronic renal failure [4].

High impact information on Sch 33861

The synthesis of spirapril (5), spiraprilat (25), their RSS stereoisomers, and their glycyl (18b) and lysyl (36, 37) analogues is described [5].
However, the bioavailability of spiraprilat and hypotensive effect of spirapril were reduced in patients [3].
Effects of spiraprilat, an angiotensin-converting enzyme inhibitor, on anesthetized dogs in a new model of acute left ventricular failure [6].
Under a normal sodium diet, spiraprilat, 1 mg/kg, induced significant (at least P less than 0.05) decreases in mean arterial pressure (MAP, -11%), total peripheral resistance (TPR, -21%), left ventricular end diastolic pressure (LVEDP, -15%) and increases in heart rate (HR, +12%) and cardiac output (CO, +16%) whereas dP/dtmax remained unchanged [7].
In contrast, there were significant perturbations in the pharmacokinetics of spiraprilat: The maximum plasma concentration (Cmax) values in the severely renally impaired group were 2-3 times those in the group of patients with normal renal function whereas the corresponding area under the curve (AUC) values were 5-6 times higher [8].

Analytical, diagnostic and therapeutic context of Sch 33861

After intravenous infusion of spiraprilat, the disposition was biphasic with half-lives of 2 hours and 35 hours, respectively [9].

References

Spirapril. A preliminary review of its pharmacology and therapeutic efficacy in the treatment of hypertension. Noble, S., Sorkin, E.M. Drugs (1995) [Pubmed]
Pharmacokinetic-pharmacodynamic model relating spiraprilat plasma concentrations to systemic and regional hemodynamic effects in congestive heart failure. Bellissant, E., Chau, N.P., Thuillez, C., Gerbeau, C., Richard, C., Giudicelli, J.F. J. Cardiovasc. Pharmacol. (1997) [Pubmed]
Pharmacokinetics and haemodynamic effects of a single oral dose of the novel ACE inhibitor spirapril in patients with chronic liver disease. Krähenbühl, S., Grass, P., Surve, A., Kutz, K., Reichen, J. Eur. J. Clin. Pharmacol. (1993) [Pubmed]
Pharmacokinetics of spirapril and spiraprilat in patients with chronic renal failure. Stein, G., Sierakowski, B., Grass, P., Haufe, C.C., Jansa, U., Weidinger, G. Blood pressure. Supplement. (1994) [Pubmed]
Angiotensin converting enzyme inhibitors: spirapril and related compounds. Smith, E.M., Swiss, G.F., Neustadt, B.R., McNamara, P., Gold, E.H., Sybertz, E.J., Baum, T. J. Med. Chem. (1989) [Pubmed]
Effects of spiraprilat, an angiotensin-converting enzyme inhibitor, on anesthetized dogs in a new model of acute left ventricular failure. Nakazawa, M., Ishihara, T., Takahashi, Y., Okuhira, M., Imai, S. J. Cardiovasc. Pharmacol. (1993) [Pubmed]
Hemodynamic and cardiac effects of spiraprilat in normal and sodium depleted conscious dogs. Gérard, J.L., Pussard, E., Berdeaux, A., Giudicelli, J.F. Fundamental & clinical pharmacology. (1990) [Pubmed]
Pharmacokinetics of spirapril in renal impairment. Meredith, P.A., Grass, P., Guitard, C., Elliott, H.L. Blood pressure. Supplement. (1994) [Pubmed]
Spirapril: pharmacokinetic properties and drug interactions. Grass, P., Gerbeau, C., Kutz, K. Blood pressure. Supplement. (1994) [Pubmed]

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