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Pharmacokinetics and haemodynamic effects of a single oral dose of the novel ACE inhibitor spirapril in patients with chronic liver disease

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Summary

The pharmacokinetics and haemodynamic effects of orally administered spirapril, a novel angiotensinconverting enzyme (ACE) inhibitor, have been investigated in patients with liver cirrhosis (n=10), in patients with chronic, non-cirrhotic liver disease (n=8) and in a control group of healthy subjects (n=16).

The absorption and elimination of spirapril did not differ between patients with liver disease and control subjects. In contrast, the bioavailability of spiraprilat, the metabolite responsible for the pharmacological action of spirapril, was significantly reduced in patients (AUC 820 μg·h·l−1, 923 μg·h·l−1 and 1300 μg·h·l−1 in patients with cirrhosis, patients with non-cirrhotic liver disease and in healthy subjects, respectively.

Compared to healthy subjects, cirrhotic patients had a reduced rate constant of spiraprilat formation (1.10 h−1 in patients vs. 2.00 h−1 in control subjects) while the elimination half-life of spiraprilat was not different. The effect of spirapril on diastolic blood pressure was decreased in patients with chronic liver disease as compared to the controls.

Thus, the pharmacokinetics of spirapril was unchanged in patients with different types of liver disease, including cirrhosis. However, the bioavailability of spiraprilat and hypotensive effect of spirapril were reduced in patients.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, University of Berne, Switzerland

    S. Krähenbühl & J. Reichen

  2. Human Pharmacology Department, Drug Safety Assessment, Sandoz Pharma, Basle, Switzerland

    P. Grass & K. Kutz

  3. Sandoz Research Institute, East Hanover, NJ, USA

    A. Surve

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  1. S. Krähenbühl
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  2. P. Grass
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  3. A. Surve
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  4. K. Kutz
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  5. J. Reichen
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Krähenbühl, S., Grass, P., Surve, A. et al. Pharmacokinetics and haemodynamic effects of a single oral dose of the novel ACE inhibitor spirapril in patients with chronic liver disease. Eur J Clin Pharmacol 45, 247–253 (1993). https://doi.org/10.1007/BF00315391

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  • DOI: https://doi.org/10.1007/BF00315391

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