2010124

87449

IF2008

100KN
200KN
OZAGREL Tablets 100KN200 KN

100KN1100mg
200KN1200mg

(JAN)
Ozagrel Hydrochloride Hydrate(JAN

100KN 2010715

20101119

20101216

200KN 2003314

2003 7 4 2003 7 4

TEL0776-73-0911 FAX0776-73-0821
http://www. kobayashikako. co. jp

IF201012(7)

http://www.info.pmda.go.jp/

63 2
IF IF
10 9
3 IF
10
20 9
IF

2
IF

IF
IF

IF
A4 9

IF
IF
2
IF
IF
IF IF
IF

 2008IF 2008
IF
PDF
IF
IF 2008 21 4
IF 2008

IF

3
IF 2008 MR PDF

IT MR

IF

IF IF
MR IF

IF

IF

4
IF

IF

IF

2008 9

11
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(1)
2009411
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CAS 2

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(1) 12
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(3)12

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(7) 16
16
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(1) 16
(2) 16
(3) 16
(4) 16
(5) 16
17
(1)17
(2)(CYP450)
17
(3)17
(4)17
(5)17

5
(1) 5
(2) 5
(3) 5
(4)pH
pH 5
5
(1)() 5
(2) 5
(3) 5
5
6
7
7
7
10
10
10 10
11 10
12 10
13 10
14 10

11

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(1) 17
(2) 17
(3) 17
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1624
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(3) 19
(4)
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(5)
19
(6)
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20
10 20
11 20
12 20
13 20
14 20
15 20
16 20

25
25

26
26

27
128
229

21
(1)
. 21
(2) 21
(3) 21
(4) 21
21
(1) 21
(2) 21
(3) 22
(4) 22

23
23
23
23
(1) 23
(2)
23

(2)

200KN()481(1148)
2003(15)3
71
100KN()0331015(
17331)2010
(22)712(2)
100KN200KN

()

(1)
100KN
200KN
(2)
OZAGREL Tablets 100 KN
OZAGREL Tablets 200 KN
(3)

(1)
(JAN)
(2)
Ozagrel Hydrochloride Hydrate (JAN)
ozagrel (INN)
(3)1)
-grel-

C13H12N2O2HClH2O
282.72

(E )-3-[p -(1H -imidazol-1-ylmethyl)phenyl]-2-propenoic acid hydrochloride monohydrate

KOZA(T)

CAS
78712-43-3(Ozagrel Hydrochloride)
82571-53-7(Ozagrel)
2

(1)

(2)

(95)

pH2)
37

mg/mL

pH1.2

154

pH4.0

211

pH6.8

238

181

pH8.0

212

*McIlvaine
(3)

(4)
227233
(5)2)
pKa3.86
pKa6.62
(6)

(7)
34000
269273nm

2)

376
(pH)pH1.2pH4.0pH6.8pH8.0376
pH1.2pH4.0pH6.8pH8.01,000lx37
6


(1)
(2)
(3)()
(4)

()

271nm

(1)

100
KN

200
KN

7.1mm

3.2mm

131mg

9.1mm

4.0mm

260mg

1

100mg

1

200mg

(2)

(3)

PTP

100KN

KN
313

KN313 100mg

200KN

KN
415

KN415 200mg

(4)pHpH

(1)
100KN1100mg
200KN1200mg
(2)

100KN

400

200KN
(3)

3)
100KN

*1

*1

0.001

0.001

25 75 RH

40

()

30.233.8

27.932.5

4545-75%

54.661.0

53.059.0

12075% 98.5102.3

91.3101.3
*1

0.001

0.001

0.008

0.008

0.062

0.064

1515-45%

30.233.8

27.733.6

4545-75%

54.661.0

51.558.6

12075% 98.5102.3

90.2100.1

(%)

98.9

99.3

*1

*1

0.001

0.001

0.008

0.007

0.062

0.070

1515-45%

30.233.8

31.433.3

4545-75%

54.661.0

55.458.0

12075% 98.5102.3

99.9103.2

(%)

98.9

98.4

*1*2

*1*2

*3

*3

*4

*4

1515-45%

25.435.5

26.233.4

4545-75%

49.562.4

51.058.9

12075% 90.2102.9

94.3102.7

4075RH

1515-45%

99.5

50

()

0.068

*1

PTP

0.008

0.062

98.9

(120
Luxhr)

0.008

(%)

(%)

98.7102.2

98.4101.0

*1*2

*1*2

*3

*3

*4

*4

1515-45%

25.435.5

26.635.1

4545-75%

49.562.4

51.160.5

12075% 90.2102.9

85.2101.7

(%)

98.7102.2

98.1102.0

*1
*2

9.

*3(JP15) 2.
*4
4075%RH6100KN
3
6

200KN

25 75 RH

4075RH

()

N.D.

N.D.
N.D.

0.5%

0.021

0.017

(%)

100.9

101.3

*1

*1

40.2%

N.D.

N.D.

(60 0.1%
Luxhr)
0.5%

0.007

N.D.

0.021

0.018

()

PTP
()

*1

0.007

(%)

100.9

100.5

*1*2

*1*2

(%)

99.599.8

99.7100.0

PTP

*1

40.2%

25

0.1%

*1*2

*1*2

(%)

99.599.8

99.6100.9

*1*3

*1*3

1510-40%

22.828.3

4540-70%

45.557.9

99.7104.1

98.7100.1

99.8100.5

12085%
(%)

*1
*2

9.

*3
3200KN
3

4)

100KN
100KN
200KN
()
200KN
487(91222)
1124004(18
1124)


(JP13)
900mL370.5
pH1.2 1
pH4.0McIlvaine
pH6.8 2

50rpm
100rpm

(50rpm)(100rpm
40%85%2
15%

200KN

200KN
(200mg
n=12

pH1.2
50

pH4.0
50

100
80

60
40

20

100
80

60
40

20

0
30

60

90

120

pH6.8
50

30

60

90

120

50
100

80
60

40
20

40
20

100

80
60

30

60

90

120

30

60

90

120

pH1.2
100

100

80
60

40
20
0
30

60

90

120

pH1.2
pH4.0

50min-1
pH6.8

100min-1

pH1.2

200KN

200mg

(%)

(%)

30

39.8

36.5

90

80.2

79.6

30

46.4

41.9

90

91.2

88.7

30

43.9

39.8

90

85.6

87.1

30

43.2

40.1

90

85.7

85.7

30

49.0

46.7

90

92.6

91.7

n12

100KN
3

50min-1
900mL
151545
454575
12075

1525.435.5(n=18)
4549.562.4(n=18)
12090.2102.9(n=18)
9

200KN
3

50min-1
900mL
151040
454070
12085

1518.326.2(n=18)
4542.557.1(n=18)
12097.6104.3(n=18)

(1)
(2)(2)
(3)

10
()

272nm

11

12

13

14

10

1400mg(100mg4200mg2)
2

(1)20094

(2)

(3)

(4)

(5)
1)

2)

3)

4)

(6)
1)

2)

11


5)
A2
TX

(1)6)
A2

(2)

6)

I2
E25-in vitro)
A
1)A2
2)PAF
FMLP

A2

1)D

2)RAFFMLP

3)

1)

2)CPAF
(3)

12

(1)

(2)7)

Tmax(hr)

200KN

200mg

1.20.3

MeanS.D.n=14
(3)7)

100KN
64(12
214)
1124004(181124)

(JP15) ()
900mL

370.5

50min-1

(1)
40 85 2
10%
(2)

15% 12 1 25%

13


100KN200KN

100KN

100KN
200KN

100

80
60
40
20
0
15

30

45

60

90

120

100KN

100KN

(200KN)

(%)

(%)

30

45.0

39.9

90

89.9

84.6

()

50min-1

(n=12)

()

100KN

50min-1

120

(%)
101.0101.0101.4101.2100.4102.5
98.2100.9100.398.3100.299.4

(%)S.D.

100.41.25

(n=12)

200KN
487(91222)
1124004
(181124)
200KN1(200mg)22
150mL
70.51.523488

AUCCmax90log(0.8)
log(1.25))
14

2
1.5

0.5

(g/mL)
0

200KN
200mg
MeanS.D.n=14

0.5 1 1.5 2

4
hr

AUC8hr
(ghr/mL)

Cmax
(g/mL)

Tmax
(hr)

T1/2
(hr)

2.540.68

1.410.40

1.20.3

0.80.1

200mg 2.680.51

1.330.37

1.10.2

1.10.7

200KN

(MeanS.D.n=14)
AUCCmax

(4)

(5)
.() 7.
(6)()

(1)

(2)

(3)

(4)
200KN
Kel0.92710.16302n=14
(5)

15

(6)

(7)

608)

8)

(1)

8)

304/10014C-
30mg/kg
(2)

8)

301/5014C-
30mg/kg
(3)

8)

304014C-
30mg/kg
1
8.83geq/mL240.18geq/mL
(4)

(5)

8)

30
14C-30mg/kg

16


(1)8)

8)

(2)CYP450

(3)

(4)

(5)

(1)

8)
(2)

8)
200

M-1
M-2

(%)
()
04
38.1
18.2
7.9
64.1

08

024

048

40.0
24.9
9.5
74.3

40.0
25.0
9.7
74.6

40.0
23.6
9.5
73.0

(3)

8)
4874.6%8

17

(1)
(2)

(1)

(2)

(3)

(4)

(5)

(1)

18

(2)

(1)

(2)

(3)

AST(GOT)ALT(GPT)

(4)

(5)

19

(6)

(2)

10

(1)

(2)
1000mg/kg

11

12

13

14

PTPPTPPTP

15

16

20

(1)
(2)

(3)

(4)

9)
A50IC50
421nmol/L
PGI2PGE251mol/L
(in vitro)
LTC4RAF

B2A2

(1)

9)
50

(mg/kg)

>5,000

4,074

3,844

6,840

6,620

1,929

1,980

2,049

2,314

503

552

714

727

(2)

9)

501005001500mg/kg3500mg/kg
Na+K+Ca1500mg/kgCa
1003001000mg/kg3
APTT1000mg/kg

21


301003001000mg/kg52100mg/kg
pH300mg/kg1000mg/kg

30100300mg/kg52300mg/kg

300mg/kg

(3)

9)
Seg1000
2000mg/kgSegSeg
Seg

Seg600mg/kg

(4)

9)

22

100KN
200KN

(1)

(2)
14.

100KN
100
200KN
PTP100(1010) 500(1050)

PTP
(PVC)()
(PE)()

(PP)
(PE)

100mg200mg100mg200mg

23

10

100KN

2010715

22200AMX00465000

200KN

2003314

21500AMZ00295000

11

100KN

20101119

200KN

200374

12

13

14

15

16

HOT(9)

100KN

120119201

4490012F1042

622011901

200KN

115220302

4490012F2049

620000023

17

24

1) 2004
2)()(Orange BooK)No.25
3)
4)
5)JAPAN DRUGS 20082009462
6) 2010639
7)
8)[]842
9) 44 230

25

26

0331015(1148)
487(91222)

1124004(181124)

64(12214)

27

1
481 ( 11 4 8 )

1
2

1
2
3
1
2
3
4
5
6
7
1

2
1
2
3
4
5

28

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