Abstract
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.
Original language | English (US) |
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Pages (from-to) | 48-56 |
Number of pages | 9 |
Journal | Journal of Clinical Pharmacology |
Volume | 58 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2018 |
Keywords
- angiotensin II receptor blocker
- azilsartan medoxomil
- drug metabolism
- hepatic impairment
- hypertension
- pharmacokinetics
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)