????????

1
??????????????????????????????????????????2007
?12?3?

• NPO?????????????(??????)
• ? ??
• ?543-0062 ?????????3-2-17 902
• TEL [phone] FAX [phone] URL
  http//www.npojip.org
• e-mail gec00724_at_nifty.com

2
2005.2.25 ????
3
??????
4
2005? 11?12?
5
??????????
6
???????????? (2007.6.16??)
???(???)??? ???(???)??? lt10 10? ?? ??
1.??? 1.???
a ??? 18 0 32 50
b ??????? 0 5 3 8
12 ???????/??? 4 4
2.??? 2.???
a ?????,???,MOF 1 8 9
b ????? 1 1
3.?????? 3.?????? 5 5
4.???(??????) 4.???(??????) 3 3
? ? ? ? 19 5 56 80
???????????
???????????(OCB)???
7
??????????????(1)???????????????????????

• 1.????????????????
• ???????????(NSAIDs???)???
• ?????(?????????)?NSAIDs???
• ????????(???????????)
• ???????????????????????
• 2.??????????
• ???/????????
• ??????,???????????????
• ?????????????????????

8
????????????????????????
??4??????????????????????????????? ???????????????
??40????????????????? ??????????????????????????
9
??????????????????????????

• ??????????????????????????????????????????
• ??1??????????????????????????????
• ??2.???,????????????,???????????????????????(cyto
  kine storm).
• ??3.??????????????????????
• cytokine storm??????????.
• ????????????????????????????????????(BBB)??????

10
??????????????(2)???????????????????????

• 3.???????
• 1)??????????????????
• ???,????,??????????????
• 2)BBB???????????(P-?????)
• 3)BBB????????????????????????
• 4)dyscontrol(???)?????/??????
• 4)??????????(?????)????????
• ???????????????????????????
• 5)???(OCB)????????????????(????????)???
• ???????????????????????????
• 4.??????????????????
• 1)?????,??,????????????????
• 2)?????????????????????
• 3)?????????????????45??(??)
• 4)????????????(???)???????

11
????????(01.207.5.31)

• ???(???) 1377?
• ?????????567?
• (???????211?)
• ??71?
• (?????????????80?)
• ????????12?????

12
??????????????????????

• ??????????(01.3)?1?(60????????????????????????????
  ???????????)
• ??????3???????????????????1??????????????
• ?????(2002.9)???????????? ????????????2??2?????
• ?????50??????????????????10??7?????(?????1????)?

13
??1(????????)

• 2002?12?3?????(BW13.5kg). 02.12
  A????39.6?.????????????A??????????????50mg??,???
• 14???????????27.5mg(2mg/kg)???
• ????15??????????
• 16??(?2???)??????????????????????B???1715???
• ??????????(????)?
• ?????(???????),microgliosis,??????????????????????
  ????????

14
??2 (??????)

• ?????39????05?2? 1930?C?????37.5??B??????????????
  ???500mL??,?????500mg???
• ??????????????2?????????22?????
• ????????????????????C????????D????????
• ????????3???(??????3???)?????????????(448g,??????
  ?),???(????),?????-?????,?????????????????????????
  ????????????????
• ??2????????????????????????????

15
????? ???? ??

• 0??(16.5mg/????8kg???????????)
• ???????????????????????????1????
• ???????FluB???????33mg/?,2?????????
• 3??,1030?????????,?????????????????????????????30
  ??????????, ???????????5?????MDZ1mg???JCS300.
• ??ICU????????????????,?????????????????,????????,?
  ?????,???????????????????(30mg/kg)????(CMZ)???
• ???????????????????????AB(-)?
• ??????????CT?MRI?????????
• ????4?????????????5?????????
• ??1??????(???????????)???
• ???????????????????????????
• ???????(?????)????????(??)???????????(????????????
  ????)

16
??3(????????????)

• 10??????????????
• ??????????????12????2??38.6????????18mg???
• ???????50???????????????????????????25????????????
  ????????????10????????1.5????????????????????????
• 5????????????????????????
• 2???????????2?11??10m????????????????????????????
• 06?4?,C???MRI?????????????????????????QTc0.397?(4?
  ???)?
• ???????????????????????

17
??4(???????????)

• 14????05.12.31?39???????????A????????????1??????8?
  ??????????9???(??39.6?)??2????????(?????)?1???????
  ??????????????????????????????????????????????????
  ???????????????????????????????????????????????37.
  5??
• ??????????????drowsy??????38.8?????(1?1?145?)???
  ??????????1??????(??3???)?????????????????????????
  ??????????(????)? ?????36.7?(2????????7???)?
• ?????????1???2?????????????(1?????????????????????
  ?????????2??????????????????????)?
• ?????????(2?????15???)????????????????????????????
  ???????

18
???????????????? (??????????)

• ???????????? (??????????????)
• ??????????
• ???????,???????2???????????
• ??????????????????????????
• ?????????????????????????
• ???????????1?????????
• ?2??????????????????????
• ???/????/?????/???????(??????)
• ????????????????????
• ????????????????????????????????????????????
• ???????????????????????????

19
??????????????????????(????)??????

• ????(???????????)
• ???(?)?????????(?????ADR)
• ?????????????????
• ??????1W3M??????(?????)
• ??????????????(???????)
• ????????????????
• ?????????????????????????????(?????????202??2004)
  
• ???????????(???????)

20
???????????????
21
????????????????(?FDA)
?? (n101) 1.5-90?????12 -16?68?17-20? 8?21?25
? (n101) ?32??69 / ?95??5??2???????1 ?32??69 / ?95??5??2???????1
?????(n103) ????/???60(??2)????? 6(??1)???12????????6?????4????15 ????/???60(??2)????? 6(??1)???12????????6?????4????15
??(n103) ??3(?????),???11,??38,???1??????????50? ??3(?????),???11,??38,???1??????????50?
??????????? 1?54?1-2?75(73)? ??10? 1?54?1-2?75(73)? ??10?
?????????????(n58) lt30? 12(21)?1??24(41)?2??32(55), 4??46(79),6??53(91),??24h lt30? 12(21)?1??24(41)?2??32(55), 4??46(79),6??53(91),??24h
???????????? ????? 65? ?????? 10? 2????? 13?2?????? 9 ????? 65? ?????? 10? 2????? 13?2?????? 9
???????07/11/11??????????
22
???????
?????????????RCT???????????????NNH ?????????????RCT???????????????NNH ?????????????RCT???????????????NNH ?????????????RCT???????????????NNH ?????????????RCT???????????????NNH ?????????????RCT???????????????NNH ?????????????RCT???????????????NNH ?????????????RCT???????????????NNH
????(n517) ????(n517) ????(n515) ????(n515) ???? NNH
? ? (95????) NNH
?? 1?? 16 3.1 51 9.9 3.4 (1.9-6.1) 15
?? 2???? 32 6.2 26 5 0.8 (0.47-1.4)
?? ????? 1 0.2 8 1.5 8.1(1.04-174) 74
???????(????NAP)???????????????????? ???????(????NAP)???????????????????? ???????(????NAP)???????????????????? ???????(????NAP)???????????????????? ???????(????NAP)???????????????????? ???????(????NAP)???????????????????? ???????(????NAP)???????????????????? ???????(????NAP)????????????????????
???????????????
????RCT???
23
????????????????????????????????4-7(1)
(p20),?4-15(1)-4-15(4)(p36-35)
?????(???????)???????(18??????)??????,???(1218?
)? ??????45???(????????????)
24
?????????(?????? vs ???) (??????????)
????4?
?????5?
??12???????
????4?
????3.7?
a????????????????????????????
25
?????????(??????vs???) (??????????)

????
?????
??
????
????
26
????????????????????
??????????
????????/???2??1??, ??4/5???????
27
??????????????????? ???????(??????70???)

• ?????A???????????(-)??????????????(?????)?????????
  ????????2cap??????????400mg/?????
• ????????????????B????????O23L?PaO242.3?PaCO228.9
  SpO280?HR108?RR20?KT38.3?????????????????(???)???
  
• ????????40/????120/?????????SpO2???????????????DLS
  T???
• ????????????(???)???B?????????????????(????????)?
• ?????????????????????????

28
5????????????????????????????????????????????(
80???)

• 38?????????????????A?????2cap???3?????5???????????
  ????????????????(ALT470?BUN73.1?Cr2.88?CRP35mg/dL)
  ???????(ARDS)?????5???????????(SpO282)???????????
  ????????3?????????????????3?????????????
• ??????????(BUN20?Cr1.88mg/dL)???OCB???????????????
  ??????????(MOF)??????ARDS(MOF???)?

29
??????????????2???????

• 15????39.2????????B???????75mg2?/????????5???????
  ????????
• 6????10???????????????????????(???)??????????????
  
• ????9??(??3??)B???????CT??MRI?????????????????n.
  p.?????????(30µg/dL???11-66)?
• ?????????????????????????????????????????????????
  
• ???????15??????????14????????????(????????????)?
  
• ????????????????

30
????????????????-????(?????)
N 94 14 52 14
??????
94 14 52 14
?1??1000mg/kg 18/24??,6/18? ???????? 9?????
E/N 2/14 6/14
28/94 12/14 1/52 4/14
?????-????
Eevent????? N???????
31
????????????????????????????????????????????
?? ?? ???? ???????? (?????????a)
?? ??? ????
???? ???????????????? ??????? ????a
?? ?? ??a
?? ???????????????????????????? ???????
???? ????????? ??????? ?????????
?? ??????? ??a
?? ?? ??
32
????????????????????????????????????????????
???????? ???????? 3??????????????????39?????????????????????,?????????2??2??????,????? ?????18??9?????????????????(??????????)?
???????? ???????? ?????????? ???????????????????????????????????????????????????????????????????????????? 500mg/kg??????????????700mg/kg????1000mg/kg???????????????????????
???????? ???????? ???? ??1????????????????????????????????????????????????????????23?????????? ?????????????????????????BBB???????????????????????????????????????24???????
33
??????????????????????????????????????????????(BZD
)??????
??????? ???? ????????????? ?????? (??????) ???? ???????????????????????????
??????? ???? ???????????? ?????? (??????) ???? ???????????????????????????
??????? ???? ?????????????????????????????? ?????? (??????) ???? ???????????????????????????
??????? ???? ???????????????????????????? ?????? (??????) ???? ???????????????????????????
???????400g??????2??2000mg/kg???4??1??2???????????????????3??4?????(????)????????????(???????????)???????????(AUC?)????????????? ??RCT????????????(??)? ???????????????????? ???BZD??????????????(??????)?? ?????,???????,???,???,???????? ???????400g??????2??2000mg/kg???4??1??2???????????????????3??4?????(????)????????????(???????????)???????????(AUC?)????????????? ??RCT????????????(??)? ???????????????????? ???BZD??????????????(??????)?? ?????,???????,???,???,???????? ???????400g??????2??2000mg/kg???4??1??2???????????????????3??4?????(????)????????????(???????????)???????????(AUC?)????????????? ??RCT????????????(??)? ???????????????????? ???BZD??????????????(??????)?? ?????,???????,???,???,???????? ???????400g??????2??2000mg/kg???4??1??2???????????????????3??4?????(????)????????????(???????????)???????????(AUC?)????????????? ??RCT????????????(??)? ???????????????????? ???BZD??????????????(??????)?? ?????,???????,???,???,????????
34
?????????????????

• ?????????????/???
• ????????????????? ????????????????
• ?????????????/?????
• ????????
• ????????????????
• ????
• ?????(?????????)?????

35
??????????(1)

• 1)???????????????????????????????????????(HCE-1)??
  ??????????????????(oseltamivir carboxylateOCB)???
  (???4??3????4??1??????????????)?
• 2) ??????????????????????????-???(?????????)??????
  ?????????OCB?????????????????
• 3) ?????????P-??????????????????(3???????)?

36
??????????(2)

• 4) HCE-1??????????????????????????????????????????
  ?????????????????????????????????
• 5)??-???????P-?????(???????)??????????????????????
  ?(?????????)???????????????????????????
• 6)??12???????????????????????????????????????????
  (?)????????
• 7)P-??????????????????????????????????????????????
  ???????????????????

37
??????????(3)

• 8)?????(???,???,???,??????)???????????????????????
  ???????????????
• 9)??????????????
• (1)?????????????
• (2)?????(???????)???????
• ??? ???
• ??????????(??)
• ????(????)?? ???

38
???????????????????

• OCB(???)?????neuraminidase??
• Sialidase?????????,??????????????????/???????????
  ?????(???????)?????Key enzyme
• Sialidase??(??)?????sialidosis(????)?2????????????
  ??????????
• ??/????????????????????OCB???neuraminidase(sialid
  ase)????????????
• 45??????-???????P-??????????????????????
  P-???????????????????????????
• ?????????????????????

39
???????????????(???)

• ????????????
• ???????????????-????????????????????????????????
  
• a)???(????????)
• b)????????????(?????)
• ????????????????????????
• ???????????(OCB)
• Neuraminidase(sialidase)????????
• ???,???(MOF),???,??,???
• ???????
• TEN???????????????????(DLST????????)????????????
  ??
• ????(????)

40
?????

• ??????????????????????????????????????????????????
  ???????
• ???????????????????????????????????/????????????
• ??????????????????????????????????????????????????
  ??????????????????????
• ???????????????????????????????????????
• ??????????????????????????????????????????????????
  ??????????????????????????????????neuraminidase(si
  alidase)????????????????