Document Detail

Concentration-effect relationships and individual responses to doxazosin in essential hypertension.
MedLine Citation:
PMID:  2531605     Owner:  NLM     Status:  MEDLINE    
1. This study investigates aspects of the pharmacokinetics, pharmacodynamics and concentration-effect relationships in 10 patients with essential hypertension during acute and chronic treatment with doxazosin, an alpha 1-adrenoceptor antagonist. 2. Following the first dose of doxazosin (2 mg) there were significant reductions in blood pressure, increases in heart rate and in plasma noradrenaline, and parallel rightward shifts of the phenylephrine pressor response curves, consistent with alpha-adrenoceptor antagonism. There was no significant change in the pressor response to angiotensin II. 3. Using an integrated kinetic-dynamic model, individual blood pressure responsiveness was characterised as the fall in blood pressure (mm Hg) per unit drug concentration. Responsiveness to the first dose of doxazosin was directly correlated with the responsiveness after 1 and 6 weeks treatment although there was a systemic reduction (of approximately 30%) which occurred during the first week of treatment. 4. Neither the acute nor long-term responsiveness to doxazosin was related to age, plasma renin activity, plasma noradrenaline or the pretreatment sensitivity to phenylephrine. There was a significant relationship between responsiveness and the height of the initial (pretreatment) blood pressure. 5. Integration of pharmacokinetic and pharmacodynamic data provides a reproducible index of responsiveness which can be used to investigate the consistency of the long-term anti-hypertensive response, to identify factors which influence the magnitude of the response, and to optimise the choice of dose and dose interval.
R Donnelly; H L Elliott; P A Meredith; J L Reid
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Publication Detail:
Type:  Clinical Trial; Controlled Clinical Trial; Journal Article    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  28     ISSN:  0306-5251     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  1989 Nov 
Date Detail:
Created Date:  1990-01-16     Completed Date:  1990-01-16     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  517-26     Citation Subset:  IM    
University Department of Materia Medica, Stobhill General Hospital, Glasgow.
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MeSH Terms
Antihypertensive Agents / administration & dosage,  adverse effects,  therapeutic use*
Blood Pressure / drug effects
Dose-Response Relationship, Drug
Heart Rate / drug effects
Hypertension / drug therapy*,  physiopathology
Injections, Intravenous
Middle Aged
Norepinephrine / blood
Phenylephrine / administration & dosage,  diagnostic use
Prazosin / administration & dosage,  adverse effects,  analogs & derivatives*,  therapeutic use
Reg. No./Substance:
0/Antihypertensive Agents; 19216-56-9/Prazosin; 51-41-2/Norepinephrine; 59-42-7/Phenylephrine; 74191-85-8/Doxazosin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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