1

(hypertension) (systolic blood pressure; SBP) 140

mmHg (diastolic blood pressure; DBP) 90 mmHg[1,2]
7.5 [3]
JNC 8[1] 60 SBP/DBP 150/90 mmHg
< 60 140/90 mmHg
angiotensin II-receptor
blockers (ARBs)
angiotensin-converting enzyme (ACE) inhibitors ARB
angioedema ACE inhibitors
ARBs azilsartan medoxomil

Azilsartan medoxomil

EDARBI

Takeda Pharmaceutical Company, Japan

456.46 g/mol

C30H24N4O8

(5-methyl-2-oxo-2H-1,3-dioxol-4-yl)methyl
2-ethoxy-1-({4-[2-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)phenyl]phenyl}methyl)-1H-1,3-benzodiazole7 carboxylate

practically insoluble in water

Angiotensin II receptor blockers (ARBs)

category C (1st trimester), category D (2nd and 3rd trimesters)

(Tablet) 40 80

Azilsartan medoxomil prodrug
azilsartan

AT1 receptors competitive angiotensin II (insurmountable)

AT1 receptor ARBs

Angiotensin II saralasin
Angiotensin II bioavailability partial agonist
imidazole-5acetic acid angiotensin II losartan
1. N-benzyl
2. carboxylic acid
3. imidazole ring

Azilsartan medoxomil ARBs Miura (2013)

azilsartan medoxomil tetrazole ring candesartan cilexetil 5-oxo-1,2,4-oxadiazole
oxadiazole azilsartan Gln257

Azilsartan medoxomil product hydrolysis azilsartan
azilsartan peak plasma
concentration 1.5 3 bioavailability 58% half life 11
plasma protein > 99%
azilsartan metabolized cytochrome P450 inactive metabolite M-II azilsartan
inactive metabolite renal clearance 2.3 mL/min azilsartan
renal impairment M-II inactive metabolites
Drug interaction azilsartan azilsartan fluconazole (CYP2C9 inhibitor) AUC
40% ketoconazole (CYP3A4 inhibitor) AUC 20%

Meta-analysis Nixon RM - indirect comparison mean change
from baseline SBP DBP Valsartan Angiotensin II Recepter Blocker (ARB) Candesartan, Irbesartan, Losartan,
Olmesartan Telmisartan Valsartan 160 320 mg (SBP) Losartan 100 mg
(3.31 mmHg, 95% CI 0.86 to 5.79 3.84 mmHg, 95% CI 1.34 to 6.31 )

ARB Azilsartan

azilsartan medoxomil
(Add on therapy) primary hypertension stage 2 20
Randomised controlled trials (RCTs) 8 8 azilsartan medoxomil
placebo active drug valsartan, olmesartan medoxomil ramipril azilsartan medoxomil/
chlorthalidone olmesartan medoxomil/ hydrochlorothiazide 4 active drug

White WB , Sica D
White WB azilsartan medoxomil valsartan 320 mg olmesartan medoxomil 40 mg
baseline 24-hour mean systolic BP 145 mmHg 6 change in 24-hour systolic BP
azilsartan medoxomil 80 mg -14.3 mm Hg, valsartan -10.0 mmHg olmesartan -11.7 mm Hg azilsartan medoxomil 80
mg valsartan olmesartan (P<0.001) azilsartan medoxomil 40 mg (non-inferior)
olmesartan clinic systolic BP azilsartan medoxomil 40 mg 80 mg valsartan olmesartan
(P<0.001) Sica D 24 change in 24-hour systolic
BP azilsartan medoxomil 80 mg -15.3 mm Hg, valsartan -11.3 mmHg azilsartan medoxomil 80 mg
valsartan (P<0.001) Azilsartan medoxomil 40 mg change in 24-hour systolic BP
-14.9 mm Hg valsartan (P<0.001) clinic systolic BP azilsartan medoxomil
40 mg 80 mg 14.9 mmHg 16.9 mm Hg valsartan (P<0.001)

William C
William C one-daily fixed dose combination azilsartan medoxomil/chlorthalidone 40/25 mg
80/25 mg olmesartan medoxomil/ hydrochlorothiazide 40/25 mg primary hypertension SBP
12 azilsartan medoxomil/chlorthalidone clinical SBP olmesartan/ hydrochlorothiazide
(P<0.001) 40/25 mg -5.3 mmHg (-7.6 to -3.1 mmHg) 80/25 mg -6.9 mmHg (-9.2 to 4.6 mmHg)
Ambulatory BP azilsartan medoxomil/Chlorthalidone Ambulatory BP -33.9 + 0.8 -36.3+0.8

olmesartan/hydrochlorothiazide (-27.5+0.8) 24
(P<0.001)

Bonner G
Bonner G azilsartan medoxomil angiotensin receptor blocker ramipril
angiotensin converting enzyme inhibitor randomised, double-blind multicenter azilsartan medoxomil
40 mg 80 mg Ramipril 10 mg systolic blood pressure (SBP) SBP 150 180 mmHg
22 azilsartan medoxomil 40 mg 80 mg clinic SBP 20.60+0.95 21.2+0.95 mmHg
ramipril clinic SBP 12.20+0.95 mmHg azilsartan medoxomil
Ramipril (p<0.001)
azilsartan medoxomil Chlorthalidone
primary hypertension stage 2 ()

1 azilsartan medoxomil

ADR

Study

Any adverse events (%)

Adverse events leading to
discontinuation (%)
Serious adverse events (%)
Deaths (%)
Most common side effect
Dizziness (%)
Headache (%)
Fatigue (%)
Serum creatinine increased (%)
Diarrhea (%)
High uric acid (M >10.5
mg/dL; F >8.5 mg/dL) (%)
Blood uric acid increased (%)
Dyslipidemia (%)
Other side effect
Cough (%)
Increase in blood creatine
kinase (%)
Nasopharyngitis (%)
Back pain (%)

Weber
et.al.
48.4

M, Bonner
et.al.
43.7

G, White
et.al.
51.1

WB, William C,
et. al
71.3

Sica D, et.al. Sica D, et.al. George L, George L,

2011.
2012.
et.al. 2011.
et.al. 2012.
65.4
49.0
41.2
52.3

1.1

13.3

2.8

14.8

8.2

3.9

9.3

1.1
-

4.1
0

1.1
-

2.8
-

2.4
0.3

1.9
-

2.8
0.4

2.0
0.3

1.6
5.8
3.2

2.7
4.1
-

3.6
6.2
2.5
1.1
4.2

16.5
5.4
9.3
3.4
-

8.8
10.1
4.3
-

4.6
7.4
4.7
-

2.8
5.6
-

12.3
5.3
3.6
12.9
-

19.3

4.7

5.4
-

9.7
-

5.6

4.1

3.1

6.5
3.8

3.7
-

ADR

Weber

Study

M, Bonner

G, White WB,, William C,

Sica D, et.al. Sica D, et.al. George

L, George

et.al.

et.al.

et.al.

et. al

2011.

2012.

et.al. 2011.

et.al. 2012.

Asthenia (%)

3.0

Arthralgias (%)
Increase in

3.0

2.4

Hypotension (%)

2.0

3.4

2.3

Edema (%)

2.7

1.8

Syncope (%)

0.5

2.0

3.2

Normal to decrease K+ (%)

1.3

Normal to increase K+ (%)

1.3

Normal to decrease Na+ (%)

0.6

Urinary tract infection (%)

3.2

8.0

Confusion (%)

2.4

Increase blood CPK (%)

4.0

g-glutamyl

transferase (%)

Upper

respiratory

tract

infection (%)
Potassium: shifts from normal
to below normal
(<3.4 mmol/L) (%)

CPK : creatine phosphokinas

L,

10

Randomize
control trial 8
Serum
creatinine

Azilsartan medoxomil angiotensin II-receptor blockers (ARBs)

25 ..2554
azilsartan medoxomil
58%
15-30% azilsartan medoxomil
chlorthalidone mild to moderate hypertension
azilsartan medoxomil (clinical outcome)
(ultimate outcome)
azilsartan
medoxomil

11

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