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) |
|---|---|
| Journal | Journal of Clinical Pharmacology |
| DOIs | |
| State | Accepted/In press - 2017 |
Fingerprint
Keywords
- Angiotensin II receptor blocker
- Azilsartan medoxomil
- Drug metabolism
- Hepatic impairment
- Hypertension
- Pharmacokinetics
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
Cite this
Single-Center Evaluation of the Pharmacokinetics and Safety of the Angiotensin II Receptor Antagonist Azilsartan Medoxomil in Mild to Moderate Hepatic Impairment. / Dudkowski, Caroline; Karim, Aziz; Zhao, Zhen; Alonso, Alberto B.; Garg, Dyal; Preston, Richard A.
In: Journal of Clinical Pharmacology, 2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Single-Center Evaluation of the Pharmacokinetics and Safety of the Angiotensin II Receptor Antagonist Azilsartan Medoxomil in Mild to Moderate Hepatic Impairment
AU - Dudkowski, Caroline
AU - Karim, Aziz
AU - Zhao, Zhen
AU - Alonso, Alberto B.
AU - Garg, Dyal
AU - Preston, Richard A
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Angiotensin II receptor blocker
KW - Azilsartan medoxomil
KW - Drug metabolism
KW - Hepatic impairment
KW - Hypertension
KW - Pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=85026429162&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85026429162&partnerID=8YFLogxK
U2 - 10.1002/jcph.970
DO - 10.1002/jcph.970
M3 - Article
C2 - 28750149
AN - SCOPUS:85026429162
JO - Journal of Clinical Pharmacology
JF - Journal of Clinical Pharmacology
SN - 0091-2700
ER -