Pharmacodynamic, pharmacokinetic and humoral effects of oral zabicipril, an angiotensin converting enzyme inhibitor in normotensive man.

  title={Pharmacodynamic, pharmacokinetic and humoral effects of oral zabicipril, an angiotensin converting enzyme inhibitor in normotensive man.},
  author={Natalie J Macdonald and Daniel M. Hughes and Kennedy R. Lees and John L. Reid},
  journal={British journal of clinical pharmacology},
  volume={30 1},
1. Zabicipril, S9650, a new angiotensin converting enzyme inhibitor, was administered to salt-replete, normotensive males in single doses of up to 10 mg. 2. The safety, tolerance and dose-response relationship with regard to inhibition of plasma ACE activity were characterised initially in an open, pilot, dose-finding study in 12 subjects and further explored in a double-blind, parallel group, placebo controlled study in another 30 subjects. 3. The drug was generally well tolerated and produced… 
6 Citations
Pharmacokinetic-pharmacodynamic model relating zabiciprilat plasma concentrations to brachial and femoral haemodynamic effects in normotensive volunteers.
As zabiciprilat peak plasma concentrations average 20 ng ml(-1) after the 2.5 mg dose of zab anticipril, this dose of the drug should be sufficient to induce optimal haemodynamic effects.
Pharmacokinetic-pharmacodynamic model relating lisinopril plasma concentrations to regional hemodynamic effects in healthy volunteers.
The concentration-effect relations for BVR (or BAF) and PCEA display quite different shapes (CE50, gamma), which emphasizes the necessity of performing pharmacokinetic-pharmacodynamic (PK-PD) modeling on hemodynamic parameters to determine the optimal dosages of ACEIs.
Pharmacokinetic-pharmacodynamic model relating spiraprilat plasma concentrations to systemic and regional hemodynamic effects in congestive heart failure.
In severe CHF, a 30 ng/ml plasma concentration is mandatory to normalize PCWP and BBF, which corresponds to the peak achieved after a 6-mg oral dose of spirapril.
Systemic and regional hemodynamic effects of zabicipril in healthy volunteers
Although it did not affect the systemic hemodynamic parameters, zabicipril induced a strong peripheral vasodilation, significantly reducing brachial, carotid, and femoral resistances and increasing the corresponding blood flows from 3 or 4½ hours to 9 hours.
Angiotensin‐Converting Enzyme Inhibition Increases Exercise Tolerance and Muscle Blood Flow in Rats with Peripheral Arterial Insufficiency
It is indicated that ACE inhibition improves BF to ischemic muscles and, together with chronic physical activity, improves exercise tolerance and the results from this study support those advocating ACE inhibition in managing appropriate patients with peripheral arterial insufficiency.


Haemodynamic and humoral effects of oral perindopril, an angiotensin converting enzyme inhibitor, in man.
  • K. Lees, J. Reid
  • Medicine, Biology
    British journal of clinical pharmacology
  • 1987
Perindopril appears to be a well tolerated inhibitor of plasma angiotensin converting enzyme, with predictable effects on the renin angiotENSin system and blood pressure.
Pharmacodynamics of converting enzyme inhibition: the cardiovascular, endocrine and autonomic effects of MK421 (enalapril) and MK521.
These studies suggest that the hypotensive effect of MK421 and MK521 is due to inhibition of the renin-angiotensin system secondary to converting enzyme inhibition, which decrease blood pressure in normal subjects without reflex tachycardia.
The physiological disposition and metabolism of enalapril maleate in laboratory animals.
Enalapril maleate, the monoethyl ester of MK-422, proved to be significantly better absorbed in both rats and dogs, and was absorbed intact in dogs and converted toMK-422 after absorption.
Factors related to first dose hypotensive effect of captopril: prediction and treatment.
A severe first dose effect cannot be consistently predicted in individual patients who have received other antihypertensive drugs for severe hypertension, and patients should have close medical supervision for at least three hours after the first dose of captopril.
Panel 1: Phase I investigations
The objectives of preclinical testing are to determine target organ toxicity, to evaluate the nature and reversibility of dose-related toxic effects, and to demonstrate the maximal "no toxic effect"
A liquid chromatography-assisted assay for angiotensin-converting enzyme (peptidyl dipeptidase) in serum.
Modification of the spectrophotometric assay described by Cushman and Cheung for serum angiotensin-converting enzyme with use of "high-pressure" liquid chromatography to measure the hippuric acid end product, with presence of large quantities of lipid did not affect the accuracy of the determination.
Automatic blood pressure monitors A clinical evaluation of five models in adults
Five automatic blood pressure monitors were evaluated by comparing their values with almost simultaneous blood pressure readings from radial artery catheters, finding that popularity of the different machines rejected the degree to which the machine reproduced the behaviour of the direct pressure measurement.
Concentration effect modelling with converting enzyme inhibitors in man.