????????A(HMG-CoA) ????????????

1
????????A(HMG-CoA)????????????
HMG-CoA ??? CYP450 ??????????
???? ? 3A4/2D6 ?
???? ? 3A4 ?
???? ? ? ?
???? ? 3A4 ?
????? ? 3A4/2C8 ?
???? ? 2C9 ?
2
?????????????

• 73?????????20mg/?7????6?????(2??9g)??????????????(
  ??????)
• ??1?????1???????,????,??,??

Wong PWK et al. South Med J, 199891202-205.
3
?????????????(?)

• ??1????4????????????????
• ???????,???????,???,?????????????(???????????113mg
  /dl)
• ????????(ICU)????10?,?????

Wong PWK et al. South Med J, 199891202-205.
4
?????????(??)????????????

• ?????,6??????80mg/???????????(??CYP2D6?)
• ?????????20-80mg/??????,???????10?(?????1)
• CYP3A4???????????????????

5
?????????(??)????????????

• ?????????????????,???,????,HIV????????,???,??????
  ???(gt1?/?)
• ??????10mg/?????????????????,????,??
• ??????20mg/??????????????????,???(??CYP2D6???????
  ?)

6
????????????????

• ???4???????????,10?????????
• 20mg?????????????
• ???????????????240mg/?2????
• ?????????????(AUC)??257????????

Azie NE et al. Clin Pharmacol Ther 199864369.
7
????????????????
?????????(AUC)
1000
800 600 400 200
0
1 2 3 4 5 6 7 8 9 10 ??
Azie NE et al. Clin Pharmacol Ther 199864369.
8
????????
AB
????????
?????
??????
??????
?????
????
????
??
??? ????
Hansten PD, Horn JR. Modified from James Reason,
Human Error, 1990
9
CYP450??????????????
??? ????
CYP2C9 ?1-5??????lt2??????????????
CYP2C19 ??20?????2-5?????
CYP2D6 ??8??????1-3???????1????
Levy RH, Thummel KE, Trager WF, Hansten PD,
Eichelbaum M. Metabolic Drug Interaction,
Lippincott Williams Wilkins,2000.
10
??CYP450????????

• ?CYP450???????????????????
• CYP1A2 7?????
• CYP2C 14?????
• CYP2D6 70?????
• CYP3A4 4?????
• ?????????????????????

MacLeod SL et al. Clin Chem Lab Med
200038883-887
11
CYP2D6???????????????

• CYP2D6???????
• ??????
• 5-10????
• 1-2?????
• ?????
• ???
• ???/????
• ?????
• ????
• ????
• ????

N 88
100
80
75 50 25
46
17
0
???/ ???
???/ ???
???/ ???
Mulder AB et al. Clin Pharmacol 200170546-51
12
????????????????????????????

• 9?????(EM)????6?????(PM)?????????18.75mg??????????
  ??50mg(?????????4?)
• ???????????EM??????,??????PM????

??????
120 100 80 60 40 20 0
EM PM
?????? ????????
Lessard E et al. J Clin Psychopharmacology
200121175-184.
13
????????
AB
????????
?????
??????
??????
????
????
??
??? ????
Hansten PD, Horn JR. Modified from James Reason,
Human Error, 1990
14
?????????????
????
????
?? ?? ??/?? ?? ?? ??
?? ???? ???? ???? ???? ??
?? ???? ?????
?????
??Hanston, Science Medicine,1998516-25.??
15
????????????????

• 18????????40mg????????,??????200mg???????
• ?????????????
• ???????CYP450???(3A4,2C19,2D6)??

Gutierrez M, Abramowitz W, Pharmacotherapy
200121163-168.
16
???(???????)????

• ????????13?????????????,???????????150mcg/?
• 1????10?????????(??????????)??
• ???????,?????????
• ???????????

Costigan et al, Clin Pediatr 198423172.
17
????????????

• ??????150mcg/??49?????????????????????????
• ????????Tums(??????)????,??????Tums??????????
• ????????????,??????????????

Butner LE et al, Ann Intern Med. 2000132595.
18
????????????

• 20???????????????????
• ?????????????3??
• ?????????,???????????
• 4???????????gt????

????????
3 2 1 0
???????????
Singh N et al, JAMA 20002832822-2825.
19
????(???Norvir)????(???Xanax)-?????????-

• 8??????????1mg????,??????(48???4?)????
• ????? ?????????????(AUC)?????
• ????????????????? ???????

?????????(AUC)
600 400 200
0
?????? ????????
Greenblatt DJ et al, Clin Pharmacol Ther
200067157,Abst.
20
???????????????????

• 16???????????????3??,?????????40mg
• ?????????(AUC)????
• (??1.2-4.3?)

?????????(AUC)
200 150 100 50 0
???? ????????
Rogers JD et al, Clin Pharmacol Ther
199966358-366.
21
??????????????CYP3A4???
6