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O-36: The orally active renin inhibitor SPP100 blocks the renin-angiotensin system in humans equally well as enalapril

Nussberger, Juerg ; Wuerzner, Gregoire ; Jensen, Chris ; Brunner, Hans R.

In: American Journal of Hypertension, 2001, vol. 14, no. S1, p. 17A-17A

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    Titre
    • O-36: The orally active renin inhibitor SPP100 blocks the renin-angiotensin system in humans equally well as enalapril
    Auteur
    • Nussberger, Juerg. Division of Hypertension University Hospital, Lausanne, Switzerland
    • Wuerzner, Gregoire. Division of Hypertension University Hospital, Lausanne, Switzerland
    • Jensen, Chris. Division of Hypertension University Hospital, Lausanne, Switzerland
    • Brunner, Hans R.. Division of Hypertension University Hospital, Lausanne, Switzerland
    Type de document
    • Postprint
    Identifiant OAI-PMH
    • oai:doc.rero.ch:300439
    Summary
    The activity of the renin-angiotensin system (RAS) is mainly determined by the concentration of active renin. Direct inhibition of renin is therefore a primary goal for blocking the RAS. So far, all specific renin inhibitors lacked potency or were clinically ineffective after oral administration. We tested the new orally active non-peptidic renin inhibitor SPP100 in 18 healthy volunteers on a constant sodium diet (100 mmol/day)using a double-blind, threeway crossover protocol. In 3 periods of 8 days, separated by wash-outs of 1 week, each volunteer received 2 dosage levels of SPP100 once a day (40,80,160 or 640mg) and placebo or 20mg enalapril. SPP100 was well tolerated. Not surprisingly, blood pressure and heart rate remained unchanged in these normal volunteers. SPP100 plasma levels showed that steady state was reached after 8 days of dosing. The table below summarizes median plasma levels at peak (P, 0.5-6h) and trough (T, 24h after dosing)on day 8: In conclusion, the renin inhibitor SPP100 dose-dependently blocks the RAS and decreases angiotensin levels in human subjects following oral administration. The effect is long-lasting and at 160mg at least equivalent to that of 20mg enalapril. SPP100 has the clear potential to become the first renin inhibitor that provides a true alternative to ACE-inhibitors and Ang II receptor antagonists in the therapy of hypertension, cardiovascular and renal disease. Placebo SPP 100 Enalapril 40mg 80mg 160mg 640mg 20mg Renin pg/ml P 12 34 95 130 670 330 T 11 19 39 64 373 58 PRA ng/ml/h P 1.0 0.28 0.21 0.16 0.08 27 T 1.4 0.89 0.60 0.41 0.39 3.5 Ang I fmol/ml P 3.2 1.6 1.4 0.33 0.70 350 T 7.0 7.1 6.1 4.8 3.1 34 Ang II fmol/ml P 3.0 1.5 1.5 0.61 0.27 0.88 T 4.5 3.7 3.5 3.2 2.5 4.2