The effects of hepatic impairment on the pharmacokinetics of doxazosin

J Clin Pharmacol. 2000 Jan;40(1):67-73. doi: 10.1177/00912700022008711.

Abstract

The pharmacokinetics of doxazosin was determined in an open-label study of 12 male volunteers with hepatic impairment (stable alcoholic cirrhosis) and 12 healthy male volunteers. Participants (fasting) received a single 2 mg doxazosin tablet, and blood samples were collected over a 120-hour period. Safety assessments included laboratory and vital sign (blood pressure, pulse rate, and ECGs) measurements and recording of all reported adverse events. The mean peak plasma concentrations were 10.8 ng/mL and 12.3 ng/mL for the subjects with hepatic impairment and healthy subjects, respectively. The corresponding mean area under the plasma concentration-time curve values were 246 and 172 ng.h/mL, a 43% increase in exposure in the subjects with hepatic impairment (p = 0.02). Although the apparent oral clearance was reduced by 30% in men with hepatic impairment compared with healthy subjects (p = 0.02), the elimination halflife was not significantly changed (24 vs. 22 hours, respectively). Laboratory test results, vital signs, and the incidence of adverse events were similar for the two treatment groups. These findings indicate that the recommended dosing regimen for doxazosin is appropriate for patients with clinically mild to moderate hepatic impairment.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial

MeSH terms

  • Blood Pressure / drug effects
  • Doxazosin / adverse effects
  • Doxazosin / pharmacokinetics*
  • Electrocardiography / drug effects
  • Heart Rate / drug effects
  • Humans
  • Liver Cirrhosis, Alcoholic / metabolism*
  • Male
  • Middle Aged

Substances

  • Doxazosin