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Single-Center Evaluation of the Pharmacokinetics and Safety of the Angiotensin II Receptor Antagonist Azilsartan Medoxomil in Mild to Moderate Hepatic Impairment.

  • Dudkowski, Caroline1
  • Karim, Aziz2
  • Zhao, Zhen1
  • Alonso, Alberto B3
  • Garg, Dyal3, 4
  • Preston, Richard A3, 5, 6
  • 1 Takeda Development Center Americas, Inc., Deerfield, IL, USA.
  • 2 AzK Consulting Inc., Skokie, IL, USA.
  • 3 Clinical Pharmacology Research Unit, Division of Clinical Pharmacology Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA.
  • 4 Clinical Research Services, Inc., Boynton Beach, FL, USA.
  • 5 Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine Florida International University, Miami, FL, USA.
  • 6 Jackson Memorial Hospital, Miami, FL, USA.
Published Article
Journal of clinical pharmacology
Publication Date
Jul 27, 2017
DOI: 10.1002/jcph.970
PMID: 28750149


Azilsartan medoxomil (AZL-M) is a potent angiotensin II receptor blocker that decreases blood pressure in a dose-dependent manner. It is a prodrug that is not detected in blood after its oral administration because of its rapid hydrolysis to the active moiety, azilsartan (AZL). AZL undergoes further metabolism to the major metabolite, M-II, and minor metabolites. The objective of this study was to determine the effect of mild to moderate hepatic impairment on the pharmacokinetics of AZL and its major metabolite. This was a single-center, open-label, phase 1 parallel-group study that examined the single-dose (day 1) and multiple-dose (days 4-8) - 40 mg - pharmacokinetics of AZL and M-II in 16 subjects with mild and moderate hepatic impairment by Child-Pugh classification (n = 8 per group) and subjects (n = 16) matched based on age, sex, race, weight, and smoking status. Mild or moderate hepatic impairment did not cause clinically meaningful increases in exposure to AZL and M-II. Mild or moderate hepatic impairment had no clinically meaningful effect on the plasma protein binding of AZL and M-II. Single and multiple doses of AZL-M 40 mg were well tolerated in all subject groups. Based on the pharmacokinetic and tolerability findings, no dose adjustment of AZL-M is required for subjects with mild and moderate hepatic impairment.

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