Clinical Pharmacokinetics

, Volume 52, Issue 5, pp 347–358

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
Original Research Article

DOI: 10.1007/s40262-013-0044-y

Cite this article as:
Preston, R.A., Karim, A., Dudkowski, C. et al. Clin Pharmacokinet (2013) 52: 347. doi:10.1007/s40262-013-0044-y

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.

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Richard A. Preston
    • 1
    • 2
    • 3
  • Aziz Karim
    • 4
  • Caroline Dudkowski
    • 5
  • Zhen Zhao
    • 5
  • Dyal Garg
    • 1
    • 6
  • Oliver Lenz
    • 7
  • Domenic A. Sica
    • 8
  1. 1.Clinical Pharmacology Research Unit, Division of Clinical Pharmacology, Department of Medicine, Miller School of MedicineUniversity of MiamiMiamiUSA
  2. 2.Jackson Memorial HospitalMiamiUSA
  3. 3.Department of Cellular Biology and Pharmacology, Herbert Wertheim College of MedicineFlorida International UniversityMiamiUSA
  4. 4.AzK Consulting Inc.SkokieUSA
  5. 5.Takeda Global Research & Development Inc.DeerfieldUSA
  6. 6.Clinical Research Services, Inc.Boynton BeachUSA
  7. 7.Division of Nephrology, Department of Medicine, Miller School of MedicineUniversity of MiamiMiamiUSA
  8. 8.Division of Nephrology, Department of MedicineVirginia Commonwealth University School of MedicineRichmondUSA