Document Detail

Pharmacologic activity of prazosin is decreased by alpha-1-acid glycoprotein in vivo.
MedLine Citation:
PMID:  2164099     Owner:  NLM     Status:  MEDLINE    
The pharmacologic response to drugs is generally assumed to be related to the unbound concentration of the active species. This study, however, reports that the alpha-1 adrenergic blocking activity of prazosin is lower in the presence than in the absence of the plasma protein alpha-1-acid glycoprotein (AAG), at the same unbound concentrations. This phenomenon suggests that plasma proteins can modify the activity of drugs by mechanisms other than those reflected by changes in the unbound fraction values. The pharmacodynamic activity (percentage of decrease in systolic blood pressure) of prazosin was studied in control rats and in rats that were administered 40 mg/kg of human AAG. The effect vs. log unbound concentration relationships were right-shifted in the presence of AAG both after intravenous bolus doses (160 micrograms/kg) and during intravenous infusion (0.6-2.4 micrograms/min/kg), i.e., AAG decreased the activity of unbound prazosin. The Emax and EC50 (mean +/- S.E.) values for unbound prazosin in control animals in the intravenous bolus study were 33.4 +/- 2.6% of the control blood pressure (zero time) and 6.2 +/- 1.4 ng/ml, respectively; and in AAG-treated animals 37.8 +/- 6.0% of the control blood pressure and 18.9 +/- 6.1 ng/ml, respectively. The EC50 value was statistically significantly increased in the presence of AAG (t = 4.97, P less than .001) whereas no difference was seen in the Emax value (t = 1.65, P greater than .1). The possible underlying mechanism(s) of the effect of AAG is discussed.
J Chiang; S Oie
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  254     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1990 Jul 
Date Detail:
Created Date:  1990-08-13     Completed Date:  1990-08-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  324-9     Citation Subset:  IM    
Department of Pharmacy, School of Pharmacy, University of California, San Francisco.
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MeSH Terms
Blood Pressure / drug effects
Orosomucoid / pharmacology*
Prazosin / metabolism,  pharmacology*
Rats, Inbred Strains
Receptors, Adrenergic, alpha / drug effects
Grant Support
Reg. No./Substance:
0/Orosomucoid; 0/Receptors, Adrenergic, alpha; 19216-56-9/Prazosin

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