Document Detail

Pharmacokinetic-pharmacodynamic relationships of alpha-adrenoceptor antagonists.
MedLine Citation:
PMID:  2574089     Owner:  NLM     Status:  MEDLINE    
Competitive alpha1-adrenoceptor antagonists are effective in the treatment of both hypertension and cardiac failure. Prazosin has both a short half-life and a short duration of action, but other related quinazoline derivatives, such as doxazosin and terazosin, have pharmacokinetic and pharmacodynamic profiles which make them potentially suitable for once-daily administration. Acute reductions in blood pressure have been correlated with plasma concentrations of prazosin but in most instances, particularly during long term therapy, there is no simple, direct relationship between drug concentration and the fall in blood pressure. Using integrated pharmacokinetic-pharmacodynamic analysis, correlations have been described not only for reductions in blood pressure during short and long term treatment but also for alpha1-adrenoceptor antagonist activity. Furthermore, this integrated approach defines the drug concentration-effect relationship in individual subjects and provides a mathematical description of response that is potentially useful for investigating the factors (both kinetic and dynamic) which influence the inter- and intrasubject variability in antihypertensive effect of alpha-adrenergic blockers. Preliminary data suggest that the long term response to treatment with prazosin and doxazosin is mainly dependent upon the height of the pretreatment blood pressure and the response to the first dose.
R Donnelly; P A Meredith; H L Elliott
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Clinical pharmacokinetics     Volume:  17     ISSN:  0312-5963     ISO Abbreviation:  Clin Pharmacokinet     Publication Date:  1989 Oct 
Date Detail:
Created Date:  1990-01-17     Completed Date:  1990-01-17     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  7606849     Medline TA:  Clin Pharmacokinet     Country:  NEW ZEALAND    
Other Details:
Languages:  eng     Pagination:  264-74     Citation Subset:  IM    
University Department of Materia Medica, Stobhill General Hospital, Glasgow, Scotland.
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MeSH Terms
Adrenergic alpha-Antagonists / pharmacokinetics*,  pharmacology
Blood Pressure / drug effects*
Dose-Response Relationship, Drug
Hypertension / drug therapy
Reg. No./Substance:
0/Adrenergic alpha-Antagonists

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