Single-dose and steady-state pharmacokinetics of doxazosin given in combination with chlorothiazide to hypertensive subjects.
The pharmacokinetics of doxazosin were determined in hypertensive subjects after a single dose of 1 mg, and at steady-state while receiving doses of 1, 2, 4 and 8 mg of the drug daily. Chlorothiazide 500 mg once daily was administered as additional therapy throughout the study. After a single dose doxazosin was rapidly absorbed, with peak plasma drug concentrations (Cmax) occurring after 2.1 +/- 0.4 hours. The elimination half-life in plasma was 10.7 +/- 1.2 hours. These parameters remained essentially unchanged during maintenance administration of doxazosin at each of the dose levels. Calculations of Cmax and area under the concentration-time curve (AUC0----infinity) indicated that the pharmacokinetic disposition of the drug remained linear over the dose range 1 to 8 mg.
Conway
E L
EL
University of Melbourne, Clinical Pharmacology and Therapeutics Units, Austin Hospital, Heidelberg, Victoria, Australia.
McNeil
J J
JJ
Meng
L
L
Drummer
O H
OH
Howes
L G
LG
Raymond
K
K
Louis
W J
WJ
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002740:Chlorothiazide / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017292:Doxazosin; D005260:Female; D006207:Half-Life; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011224:Prazosin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000959:Antihypertensive Agents; D002740:Chlorothiazide; D017292:Doxazosin; D011224:Prazosin