Single-center evaluation of the single-dose pharmacokinetics of the angiotensin II receptor antagonist azilsartan medoxomil in renal impairment
| Autor: | Caroline Dudkowski, Richard A. Preston, Domenic A. Sica, Oliver Lenz, Aziz Karim, Zhen Zhao, Dyal C. Garg |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Angiotensin receptor medicine.medical_treatment Angiotensin II receptor antagonist Pharmacology Severity of Illness Index Pharmacokinetics Oral administration Renal Dialysis Azilsartan Medicine Humans Pharmacology (medical) Prodrugs Azilsartan Medoxomil Renal Insufficiency Aged Oxadiazoles business.industry Middle Aged Tolerability Case-Control Studies Kidney Failure Chronic Benzimidazoles Female Hemodialysis business Angiotensin II Type 1 Receptor Blockers medicine.drug Follow-Up Studies |
| Zdroj: | Clinical pharmacokinetics. 52(5) |
| ISSN: | 1179-1926 |
| Popis: | 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. 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). 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. 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. |
| Databáze: | OpenAIRE |
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