??????????(????)???? (1)???????????2???? (2)????

1
??????????(????)????(1)???????????2????(2)?????
?????????????????????110???????? 2007.4.20

• ???
• NPO?????????????(?????)

2
????

• ??????????????
• (1)????????????2??
• (2)10????????????????????????????????????????????
  ???????????????????(??5?)?????????????2?????????
  ??1?(??14?)????
• ????????????????

3
??1 (??????)

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

4
??2 (??????)

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

5
????????????

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

6
??3(????????????)

• 10??????????????9?????9.0kg,??71.2cm?
• 03?1? ?????????????????????????????
• 4???????????A??????????????????????????12??????2?
  ?38.6????????A??????18mg???
• ???????50??????????????????????????75???A?????????
  ????????????????4mg???
• 10?????????1.5????????????????????????????????????

7
??3(??)

• ??????????????????????????????5??????
• ???????????(??????????????????????????????????????
  ?????)
• 1??1?3?????????????????????????1?5????????B???????
  ???????
• 2?2?????????2?11??10m????????????????????????????
• 06?4?,C???MRI?????????????????????????QTc0.397?(4?
  ???)?
• ???????????????????????

8
(2-2)??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???)????????????????????????????
  ???????

9
????????????? ??-????(?????)
N 94 14 52 14
94 14 52 14
1000mg/kg?? 18??6?? ???????? 9?????
E/N 2/14 6/14
28/94 12/14 1/52 4/14
Eevent????? N???????
10
????????????????????????????????????????????
?? ?? ???? ???????? (?????????a)
?? ??? ????
???? ???????????????? ??????? ????a
?? ?? ??a
?? ???????????????????????????? ???????
???? ????????? ??????? ?????????
?? ??????? ??a
?? ?? ??
11
????????????????????????????????????????????
???????? ???????? 3??????????????????39?????????????????????,?????????2??2?????? ?????18??9?????????????????(??????????)?
???????? ???????? ?????????? ???????????????????????????????????????????????????????????????????????????? 500mg/kg??????????????700mg/kg????1000mg/kg???????????????????????
???????? ???????? ???? ??1????????????????????????????????????????????????????????23?????????? ?????????????????????????BBB???????????????????????????????????????24???????
12
??????????????????????????????????????????????(BZD
)??????
??????? ???? ????????????? ??????(??????) ???????????????????????????????
??????? ???? ???????????? ??????(??????) ???????????????????????????????
??????? ???? ?????????????????????????????? ??????(??????) ???????????????????????????????
??????? ???? ???????????????????????????? ??????(??????) ???????????????????????????????
???????400g??????2??2000mg/kg???4??1??2???????????????????3??4?????(????)????????????(???????????)???????????(AUC?)????????????? ??????????????????????????????????????????????????????????????????????? ???BZD??????????????????????? ???????400g??????2??2000mg/kg???4??1??2???????????????????3??4?????(????)????????????(???????????)???????????(AUC?)????????????? ??????????????????????????????????????????????????????????????????????? ???BZD??????????????????????? ???????400g??????2??2000mg/kg???4??1??2???????????????????3??4?????(????)????????????(???????????)???????????(AUC?)????????????? ??????????????????????????????????????????????????????????????????????? ???BZD??????????????????????? ???????400g??????2??2000mg/kg???4??1??2???????????????????3??4?????(????)????????????(???????????)???????????(AUC?)????????????? ??????????????????????????????????????????????????????????????????????? ???BZD???????????????????????
13
????????????

• 1.????,????Epithelial Na Channel?Na/K-ATPase?dow
  nregulate????????????
• 2.???????????????????????
• 3.????????????????????????????????????????????????
  ????????
• 4.?????????????????????????????????????????????(AR
  DS????)?
• 5.???????????????????????????????????????
• 6.??????????????????????????(?????????????????????
  )????????-???????????????ARDS?????????
• 7.???????????????????????????????????????????????
  ???????????????????????????

14
???????????????(Delayed neuronal cell damage)

• ?????(1)
• ????(????)????????/??????????????????????????????
  ??????
• ???,???,?????,???????,???(????),
• ????????????,????????,
• ?????(?????????),??????????
• (????,????????????,???(?????))
• ?????(2)
• ???????129???1???????35?????116???????25?(????6?
  ????19)????
• ?????(3)
• ????12??????????,?5??????,???????????CA1????????
  ?????
• ??????????????????????????
• ???????????????????????

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

• 1.??????(???????????????)
• 2.????????????????(??1?2)
• 3.???????????X??????????????????????????(????)
• (4?4???????????????)
• 4.??????????????????????????(????????????3)
• 5.????????????????2????????????? (??4)
• 6.??????????????(???????)
• 7.??????????????????????????? (???????)

16
??3????????

• ??????????
• ?????Delayed neuronal cell damage????
• ??????????????????
• 1.ADEM(??????MRI????????)
• 2.Rett ???(????????????,?????
• ???????,??????????,????)
• 3.ALTE?????
• ?????/???????????????
• ???????????????????????
• 4. QTc?4???????0.397?(?????)
• ???????????????????????
• ????????Delayed neuronal cell damage

17
???????

• ????(????)???
• ?????????????????????
• ???-???(BBB)??????????????
• ??????BBB??????/?????????????
• ???????????????
• (1)?????????????????????????
• (2)???(??????)?????,???,??,???
• (3)?????????????????
• ?????????
• or???????? (??? or ????)
• ?????????(????)??Delayed neuronal
• cell damage(???????????)?????
• ?????????????????????

18
???(???)????? (2007.4.4??)
ADR???(???)??? lt10 10? ?? ??
???(??????) 14 29 43
???(?????????) 3 2 5
1 ??? ?? a 17 0 31 48
2 ??????? a 0 5 3 8
3 ??????????????? 4 4
4 ??????????????? 2 8 10
5 ???(???????????????) 1 7 8
? ? b 20 5 53 78
a9???(??5???)??20????????????
10??????????????????????
b?????55???????????73?????????
78?????06?11?30???????????????
????20????????????14?!
19
??(1) ????????????2?

• 1.???????(????)???????????????????????2???????????
  (????)???????????????????????????????????????
• 2.???????????????????????????????????????????????
  ??????????
• 3.????????????????????????????????????????????????
  ?????????????
• 4.????????????????????????????????????????????????
  ????????????
• 5.??????????????????????????(?????????????????????
  )????????-???????????????ARDS?????????????????????
  ?

20
??(2)??????????????????

• 1.???????(????)????????????????2??????????????????
  ????????????????????????????????????
• 2.14?????????????10???????????(??)????????????????
  ?????????????????????????
• 3.?????????? Delayed neuronal cell damage
  (?????????)??????????
• 4.????????????????????????????1???????????????????
  ??????????????????????????
• 5.????????????????????????????????????????????????
  ????????????????????????????????????

21
???????(1)

• Q1??3?????????????????delayed neuronal cell
  damage?????????????
• ?A1??????????????????????????????????????????????
  ????????????delayed neuronal cell damage????????
• Q2???????????????????????????
• ?A2??????????(NSAIDs)??????????????????????(??NSA
  IDs??)???ARDS????????????????????????????????????
  ?????????????????
• Q3??1??????????????????????
• A350mg?????????????????????????(?????????????????
  6µg/mL??????????????????????????????)?

22
???????(2)

• ??(??)??????????????????????
• ???????????????,?????????????????????????????????
  ?????
• ?????
• ?????????????????
• ??????????
• ?????????????????????????????????????????????????
  ?????????????????40???????????????????????????????
  ??????????????????????????????????????????????????
  ??1???1?????????????????????????????????????????
  ??????????
• ???????
• ?????????????????????????????????????????????????
  ???????????

23
???????(3)

• Q4???????????????????????????????????????????????
  ??????????????????????????????????????
• A4???????????????????????????????????????????????
  ??????????????????????????????????????????????????
  ??????????????????????
• ???????????????????????????????????????????????
  ??????????????????????????????????????????????????
  ??????????????????????????????????????????????????
  ????