The pharmacodynamics and pharmacokinetics of the combination of nifedipine and doxazosin.
In a single-blind study 12 normotensive men took nifedipine 20 mg (Group 1, n = 6) or doxazosin 2 mg (Group 2, n = 6), followed by the combination. Each subject attended on four 9-h study days for evaluation of the effects of single and multiple doses of the monotherapy and the effects of adding single and multiple doses of the second drug. Measurements of BP, HR, plasma drug concentrations, and apparent liver blood flow were recorded. The combination was generally well tolerated. BP was consistently lower with the combination than with either monotherapy: for example, average erect BP was 108/61 (Group 1) and 112/62 mmHg (Group 2) compared with 122/66 and 116/68 during steady-state monotherapy. The introduction of nifedipine in Group 2 was associated with a significant increase in liver blood flow at 1.5 h: 1560 vs 1050 ml.min-1 during monotherapy with doxazosin. There was no significant kinetic interaction. In particular, the steady-state AUC of doxazosin was unaffected by the addition of nifedipine: 257, 307, 301, and 256 ng.ml-1.h for the 4 study days (Group 2).
University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, UK.
R
R
Donnelly
H L
HL
Elliott
P A
PA
Meredith
C A
CA
Howie
J L
JL
Reid
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D017292:Doxazosin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000493:pharmacokinetics / Q000494:pharmacology*; D016037:Single-Blind Method
D009543:Nifedipine; D017292:Doxazosin