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2007.7 PowerPoint PPT Presentation


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????????ALT????1000U???????????????????"?????????????"?????????. ??: ???????(drug inuced liver injury, DILI),????????,???????/??????????????????????????????????????????,???????????????????? ???????????,???????????????,????????????????????????????????????????????,??????????2%,??????????

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2007.7

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2007.7


ALT1000U


drug inuced liver injury, DILI

21020


1.

2.

3.

4.

5.

6.

7.

8. ADR




900

20-40%

3-9%

Lewis JH. Drug-induced liver disease. Best Practice of Medicine. January 2000.


Sgro1997200081301

14 /100,000DILI

  • 12% 6 %

    DILI16

    Hepatology 2002;36:451-455.


, . . , 2004.3, P514


1015%


10

40

90

60


1525

50

50%

25


(1)

Michael F.Sorrell Schiffs Diseases of the Liver2003


(2)

Michael F.Sorrell Schiffs Diseases of the Liver2003




  • I

    • -OH -SH-NH2 -COOH

  • II


1P450(CYP450)

CYP450

CYP1

CYP3A4

CYP2C2

CYP450

CYP450


1P450(CYP450)

CYP450

P450CPY1A2CPY2CPY3A

P450

P450


1P450(CYP450)

CYP450

CYP450

P450

CYP450


2

2

2S

21

21



FDASFDA


P450

O2

Ca++


()

, 2-


1

1

1,

2


P450

P450

CYP450


P450

P450

CYP450


1

1

1,

2


1

1.

2.

3.

4.

5.

6.


2

1.

2.

T

3.


3

1.

2.

28

3.

4.

P450 2E1GRP94

5.




6



ALT

GGTALP


1-5

1

ALT

2~330


  • (6%)

  • ()



2000


2


1.

2.

3.

4.

5.

6.

7.

8.



1.

2.

3.

4.



1.

2.

3.

4.

5.



1.

2.

3.

4.

5.


1.

2.

3.

4.

5.

6.;

7.

B6


1.

2.

3.

4.

5.




6779



1818


1818C18

C-18

C18

18

18


1999131

20032312




%

0

40

60

80

20


Ca2+

1997.7168


*p<0.01

18H 200110929


P450

18P450II 200136(5)321 324


GSH

*

*

* p<0.05


N10

P 0.01

P

GaIN


D-GalNSOD

** p

n=10 ** p<0.001

GaIN


D-GalNNOS

* p<0.05

n=10 * p<0.05

GaIN


P450

P450

GSH

GSH


P450

O2

Ca++



GalN


MgIGGalN

() 0

() +++ +++ + ++ +++ +++ ++ ++ ++ +++ 2.4

60mg/kg ++ ++ + + +++ ++ ++ +++ + ++ 1.9*

15mg/kg +++ ++ ++ ++ +++ ++ + + ++ +++ 2.1*

30mg/kg + ++ +++ ++ ++ ++ + ++ 1.5**

60mg/kg ++ + + ++ ++ ++ + + 1.2***

N =10,* p > 0.05; ** p < 0.05; *** p < 0.01


  • 462

  • 17

    Vc

    100mg

  • 29

    Vc

  • 4


*P<0.01

#P<0.05

*

#


  • 924646226249+(DA)45mgm23d150 mgm27 d

    • l50mg+5250ml11

    • 1d8

  • ALT>45 UL


13

13

8.7

8.7

4.3

0

0

ALT1343.5 P < 0.05



Thank you!


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