Pharmacokinetic‐pharmacodynamic model relating zabiciprilat plasma concentrations to brachial and femoral haemodynamic effects in normotensive volunteers

Q2 · MEDICINE

Article

Author: Jean-François Giudicelli ; Eric Bellissant

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.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.Cγ/(CEγ50+Cγ ), 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 γ=1.0±0.4 for PCEA, Emax=55±26 ml min−1, CE50=5.1±4.0 ng ml−1 and γ=2.4±1.6 for BAF, and Emax=−45±10%, CE50=2.0±1.3 ng ml−1 and γ=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.

04 Mar 1998·Basic Research in CardiologyQ1 · MEDICINE

The arterial length-densities under preventive angiotensin-converting-enzyme inhibiting treatment in the myocardium of spontaneously hypertensive rats

Q1 · MEDICINE

Article

Author: Bock, P

The length density (Lv) of capillaries is known to be increased in the hearts of spontaneously hypertensive rats (SHR) after high-dosed but also after low-dosed subantihypertensive treatment with the ACE-inhibitor Ramipril administered in utero and post partum. Under the same conditions in the present study only high-dose Zabicipril caused an increase of capillary Lv. Under preventive ACE-inhibition in both high-dose groups Lv of myocardial arteries was significantly higher. In the low-dose groups Lv was not significantly increased. The increased arterial Lv in the high-dose-group may result from the avoidance of angiotensin II-induced overabundant growth of myocardial muscle-mass. Changes in collagen could not be found in any of the experimental groups.

01 Oct 1995·Journal of Cardiovascular PharmacologyQ4 · MEDICINE

Effect of Angiotensin-Converting Enzyme Inhibition on Intimal Thickening in Rabbit Collared Carotid Artery

Q4 · MEDICINE

Article

Author: Kockx, Mark M. ; De Meyer, Guido R. Y. ; Bult, Hidde ; Herman Arnold G.

The positioning of a nonocclusive silicone collar around the rabbit carotid artery results in the formation of a neointima under a morphologically continuous endothelium. We wished to determine whether oral treatment with angiotensin-converting enzyme (ACE) inhibitors prevents or retards intimal thickening and whether this is related to the blood pressure (BP) lowering effects of such drugs. Silicone collars were placed around the left carotid artery of 104 male New Zealand white rabbits for 14 days. The contralateral carotid artery was sham-operated. Three ACE inhibitors were administered from 7 days before collar placement until the end of the experiment: zabicipril (0, 0.03, 0.10, or 0.30 mg/kg/day), moexipril (0, 0.3, 1, or 3 mg/kg twice daily, b.i.d.), and enalapril (0 or 3 mg/kg/day). Each group consisted of 6-12 animals. BP and plasma ACE activity were measured in the nonanesthetized rabbits after 3-week treatment. To evaluate intimal thickening, we measured the cross-sectional area of intima and media. The positioning of the collar led to significant intimal thickening after 14 days. Although the ACE inhibitors decreased BP (zabicipril, 9, 16, 16%; moexipril, 10, 22, 31%; enalapril, 15%) and plasma ACE activity (zabicipril, 87, 88, 92%; moexipril, 79, 92, 93%; enalapril, 88%) significantly and dose dependently, they did not reduce intimal thickening or the cross-sectional area of the media. Angiotensin II does not play a dominant role in collar-induced intimal thickening in rabbits. Furthermore, reducing the BP of normotensive rabbits does not alter neointima formation in this model.

100 Deals associated with Zabicipril hydrochloride

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Heart Failure	Phase 2	FR	Les Laboratoires Servier SAS	-
Heart Failure	Phase 2	GB	-	-
Hypertension	Phase 2	GB	-	-
Hypertension	Phase 2	FR	Les Laboratoires Servier SAS	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

Zabicipril hydrochloride

Overview

Basic Info

Structure

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation