Does pharmacological profiling of a new drug in normotensive volunteers provide a useful guideline to antihypertensive therapy?

Details

Serval ID
serval:BIB_ABAB3BC61600
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Does pharmacological profiling of a new drug in normotensive volunteers provide a useful guideline to antihypertensive therapy?
Journal
Hypertension
Author(s)
Brunner  H. R., Waeber  B., Nussberger  J.
ISSN
0194-911X (Print)
Publication state
Published
Issued date
10/1983
Volume
5
Number
5 Pt 2
Pages
III101-7
Notes
Journal Article --- Old month value: Sep-Oct
Abstract
Similar pressor mechanisms should be active in hypertensive and normotensive subjects since hypertension is a quantitative rather than qualitative disorder. Consequently, if an antihypertensive drug is designed to specifically block a well-defined mechanism involved in blood pressure regulation, it should be possible to evaluate its efficacy rather precisely in normotensive volunteers before even administering the compound to a hypertensive patient. That this is indeed the case is illustrated by the example of angiotensin-converting-enzyme inhibitors. The magnitude of blockade that can be obtained in humans, the minimal does needed for maximal efficacy, and the onset and duration of action of the agents have all been precisely determined in normotensive volunteers. Subsequent administration to hypertensive patients merely confirmed these findings. Moreover, if the antihypertensive effect of converting-enzyme inhibitors could not be predicted in an individual hypertensive patient, this is not related to some unknown action of the drug that cannot be assessed in normal volunteers but rather to our lack of understanding of the precise mixture of pathogenetic mechanisms prevailing in any particular patient. Only the safety evaluation and the search for side-effects still has to be carried out in nonspecific fashion, thus requiring long-term observations in large numbers of patients. If the tolerance of new converting-enzyme inhibitors were more predictable, the number of studies in hypertensive patients could be drastically reduced since the antihypertensive profile of any new converting-enzyme inhibitor can probably be precisely determined in normotensive volunteers.
Keywords
Aldosterone/blood Angiotensin I/pharmacology Angiotensin II/blood *Angiotensin-Converting Enzyme Inhibitors Antihypertensive Agents/*pharmacology Blood Pressure/drug effects Captopril/pharmacology Dose-Response Relationship, Drug Drug Evaluation Humans Peptidyl-Dipeptidase A/blood Renin-Angiotensin System/*drug effects Time Factors
Pubmed
Create date
05/03/2008 16:40
Last modification date
20/08/2019 15:15
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