E Bellissant1, J F Giudicelli. 1. Service de Pharmacologie Clinique, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
Abstract
AIMS: To investigate, in healthy volunteers, the relationships between the plasma concentrations (C, ng ml(-1)) of zabiciprilat, the active metabolite of the angiotensin I-converting enzyme inhibitor (ACEI) zabicipril, and the effects (E) induced on plasma converting enzyme activity (PCEA, nmol ml(-1) min(-1)), brachial and femoral artery flows (BAF, FAF, ml min(-1)), and brachial and femoral vascular resistances (BVR, FVR, mmHg x s ml(-1)) after a single oral administration of two doses (0.5 and 2.5 mg) of zabicipril. METHODS: The study was placebo-controlled, randomized, double-blind and crossover. E was related to C by the Hill model, E = Emax x Cgamma/(CE50gamma + Cgamma), fitted to the data of both doses simultaneously. RESULTS: We obtained (mean +/- s.d.) Emax = -99 +/- 1%, CE50 = 2.2 +/- 1.0 ng ml(-1) and gamma = 1.0 +/- 0.4 for PCEA, Emax = 55 +/- 26 ml min(-1), CE50 = 5.1 +/- 4.0 ng ml(-1) and gamma = 2.4 +/- 1.6 for BAF, and Emax = -45 +/- 10%, CE50 = 2.0 +/- 1.3 ng ml(-1) and gamma = 2.3 +/- 1.4 for BVR. The parameters obtained for FAF and FVR were similar to those obtained for BAF and BVR, respectively. The CE95 (C required to induce 95% of Emax) varies from 7 to 17 ng ml(-1) for haemodynamic effects. CONCLUSIONS: As zabiciprilat peak plasma concentrations average 20 ng ml(-1) after the 2.5 mg dose of zabicipril, this dose of the drug should be sufficient to induce optimal haemodynamic effects.
RCT Entities:
AIMS: To investigate, in healthy volunteers, the relationships between the plasma concentrations (C, ng ml(-1)) of zabiciprilat, the active metabolite of the angiotensin I-converting enzyme inhibitor (ACEI) zabicipril, and the effects (E) induced on plasma converting enzyme activity (PCEA, nmol ml(-1) min(-1)), brachial and femoral artery flows (BAF, FAF, ml min(-1)), and brachial and femoral vascular resistances (BVR, FVR, mmHg x s ml(-1)) after a single oral administration of two doses (0.5 and 2.5 mg) of zabicipril. METHODS: The study was placebo-controlled, randomized, double-blind and crossover. E was related to C by the Hill model, E = Emax x Cgamma/(CE50gamma + Cgamma), fitted to the data of both doses simultaneously. RESULTS: We obtained (mean +/- s.d.) Emax = -99 +/- 1%, CE50 = 2.2 +/- 1.0 ng ml(-1) and gamma = 1.0 +/- 0.4 for PCEA, Emax = 55 +/- 26 ml min(-1), CE50 = 5.1 +/- 4.0 ng ml(-1) and gamma = 2.4 +/- 1.6 for BAF, and Emax = -45 +/- 10%, CE50 = 2.0 +/- 1.3 ng ml(-1) and gamma = 2.3 +/- 1.4 for BVR. The parameters obtained for FAF and FVR were similar to those obtained for BAF and BVR, respectively. The CE95 (C required to induce 95% of Emax) varies from 7 to 17 ng ml(-1) for haemodynamic effects. CONCLUSIONS: As zabiciprilat peak plasma concentrations average 20 ng ml(-1) after the 2.5 mg dose of zabicipril, this dose of the drug should be sufficient to induce optimal haemodynamic effects.
Authors: R J Francis; A N Brown; L Kler; T Fasanella d'Amore; J Nussberger; B Waeber; H R Brunner Journal: J Cardiovasc Pharmacol Date: 1987-01 Impact factor: 3.105