Single-center evaluation of the single-dose pharmacokinetics of the angiotensin ii receptor antagonist azilsartan medoxomil in renal impairment

Richard A. Preston, Aziz Karim, Caroline Dudkowski, Zhen Zhao, Dyal Garg, Oliver Lenz, Domenic A. Sica

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Background and objective: Azilsartan medoxomil (AZL-M) is a potent angiotensin II receptor blocker that decreases blood pressure in a dose-dependent manner. It is a pro-drug and not detected in blood after oral administration because of 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 renal impairment on the pharmacokinetics of AZL and its major metabolite. Methods: This was a single-center, open-label, phase I parallel-group study which examined the single-dose (40-mg) pharmacokinetics of AZL and M-II in 24 subjects with mild, moderate, or severe renal impairment or end-stage renal disease requiring hemodialysis (n = 6 per group), respectively, and healthy matched subjects (n = 24). Results: Renal impairment/disease did not cause clinically meaningful increases in exposure to AZL. M-II exposure was higher in all renally impaired subjects and highest in those with severe impairment (approx fivefold higher vs. control). M-II is pharmacologically inactive; increased exposure was not considered important in dose selection for AZL-M in subjects with renal impairment. Hemodialysis did not significantly remove AZL or M-II. Renal impairment had no clinically meaningful effect on the plasma protein binding of AZL or M-II. Single doses of AZL-M 40 mg were well tolerated in all subject groups. Conclusions: Based on the pharmacokinetic and tolerability findings, no dose adjustment of AZL-M is required for subjects with any degree of renal impairment, including end-stage renal disease.

Original languageEnglish (US)
Pages (from-to)347-358
Number of pages12
JournalClinical Pharmacokinetics
Volume52
Issue number5
DOIs
StatePublished - May 1 2013

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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