ti

1
???
???????pharmacokinetics
2
???????
???????? ???????ADME????????????
3
D????? DP???????
??????
4
??????????
??????
??
????
5
???
???
???????? ??????
????
???
???
6
????????
??????passive diffusion 1.????,?
? 2.???,????? 3.???,?????? 4.??????????
7
5.????????PH?? ?????????? ???????????
?????
8

• ????pH???
• ?????????(HA?B)??????
• ????????(HA?B)?????????
• ????,??????(HA?B)??????(???A-
  ?BH)?????????Ka???pH??????

?? ??????,?????????????
???pH??????????????????
9
?????
HA
H A-
A-
pH-pKa
Ka


10
HA
?pHpKa,HA A-
10
?????pKa3.4
A-
pH-pKa
1.4-3.4
1
???
10
10

HA
100
A-
???
10000
7.4-3.4
10

HA
1
11
??
??
PH 7.4
PH 1.4
HA
HA
1
1
A-
A-
0.01
10000


H
1.01
H
10001
12
???????????????,??????? ,??????????,????????
13
???????????????,???????? ,??????????,???????
14
???PH7.0,???PH7.4, ????????????,???????,????PH?,?
?????????
15
???????,??????,???????,????,????PH?,????????????
??????????????,???????????
16
???? 1.????,? ? 2.??,???? 3.???,?????? 4.???????
??
17
?????
???? ?? ??? ???
18
?????????
(?)?? absorption ????
??? ???????????
19
1????????

• ????tmax
• ????Cmax
• ?????F ???
• ?????????

20
????Cmax
??
??????????
????
???
????
??????
????
21
2??????????
1)?????? ?????????????? 2)???? ???? gt ?? gt ??
gt?? gt ?? gt ?? gt ?? gt ??
22
????
??????,?????,???
????,????,?????,???????,???????
23
?????????
???????? ???????,??????????
24
?????G(??)gt???????gt?????
25
???????????????????????????
26
???? ???????????? ?????????????
27
????
??????? ???,????????,????????,?????????????
28
????
??????? ?????,???????????????????????????????
29
?????
???????? ????,????,?????????,?????????
30
????
???? ???????????????????????????
31
3)???? ????? ?? gt ??? gt ?? gt ?? gt ????
32
4)???? first-pass elimination
???????????????????????????????
33
????
????
???
???
???
??
??
???
????
????
34
(?)??distribution
d
?????? ????
35
?????????
1.?????? ???? ????????PH
2.????? 3.????????? 4.????? ?? ??
36
????,?/??????,???????
37

• ???????,??????? ?gt?????gt?????gt??????

• ??? redistribution

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

???,???
??????,???????
??????? ????? ???? ???
39
(?)?? metabolism ???? biotransformation
40
??????
??
??????(????,??)
??
??
??? ????
??
?
?

??
41

• ????? ???
• 1. ????
• 2. ?????
• ???
• ???????

42
????(enzyme inducer) ???? ????? ????(enzyme
inhibiter) ???? ?????
43
??????????????????,?????????????,?????,??????????
????
44
????????????,??????????????,????????,????,???????
??
45
(No Transcript)
46
(?)?? excretion
47
?????
48
?? ????
?? ???? ?????
??
???????????? ?????,???? PH
???????(??? PH?,?????)
49
??
?.??????,???????,????????,(????)?????(????????)
50
?.??PH???????????,??????????????????,???????,?????
?????
51
?.??????,????????????
52
2.?? ?????? ?????-??????
??? ???? ????? ? ??? ???
53
???. ??????? ?.???????,??????,??????,??????,???(
? ???)?
54
3.?? ???????
? ????? ?? ???,?????(?????????)??????,???????????
55
??? ???? rate process ????? kinetic process
56
?????????????
??????????????(??)????????
????????????????????
57
????Cmax
????
??
????
????
????
????
58
????????????????????????. ?????AUC ???????????
59
????? elimination
kinetics

• ??????????????????????????
• ??????????
• ??????????????

60
??????
????(???? first-order kinetics)
????(??)???????????????,??????dc/dt
-KC??????????????
61
????(???? zero-order kinetics)
????(??)???????????????,dc/dt -K,????????????????
??????
62
????
????? ???? 0.2/h ?? 0 1 2 3 4 5
??100 80 64 51.2 41 32.8 mg/ml1000 800 640 512
410 328
63
????? ???? 20mg/h ?? 0 1 2 3 4
5 ??100 80 60 40 20 0 mg/ml1000 980 960
940 920 900  
t1/2??100 2.5 h 1000 50 h
64
(No Transcript)
65
t1/2
t1/2
66
?????????
????
??
????
???????
????/??
???
???
?????
??
??
??
???
?
?
?
?
??
??
??
?
?
?
?
?
67
???????(??)

• ??????????
• ???????????,???????????
• ??????????

68
???????????
1.?????bioavailability,F
AUC(?????)
???????F

100
AUC(?????)
AUC(???)
???????F

100
AUC(???)
69
????? 1).F???(????????????) ??????????????
2).F??????,?????????? 3).???????????????
70
?????F
71
2.??????(apparent volume of distribution
Vd) ??????????????? Vd(L/Kg)D(????)/ C(????)
72
?? 1?????????? 2????????????? A(????)CoVd
73
gtgt40 L
74
3.??? ( plasma half-life, t1/2) ???????????????
75
1.???????? 2.???????5?t1/2 ????????,??????5?t1/2??
????95 3.????,???????? 4.???? t1/2
76
?????????
2
0.97
0.94
1
0.875
0.75
0.5
77
?????????
?? ????
A ???? ??????
??????
B ???? ??????
C ?????? ???
D ????
78
1.????????,??????Css????????,??Css?????? 2.
??????,?Css??????????,??????,?????????? 3.????,???
?t1/2 ?Css ? 4.????ltt1/2,??????
????gtt1/2,???????,???????????????
79
???
?????????
80
????
?????????????????????(????? ???????????
81
????
1 ???? ????, ???? 2 ???? ?????
???? 3 ???? ??
82
4 ???? ????? ???? 5 ???? ??????
??????? 6 ?????????? ??? ????????
83
????????,??????? ??????????, ????????,?????????
?????????????
84
??? ??????????????, ????????(???)??????,?????,???
????????????,??????
85
??? 1.????????????,??????????
2.????????????????? 3.??????????????????????
86
4.????????????????????? 5.???????????????????????
6.???????????????
87
????mg/ml
???ml/min
????RE ??/??
???ER
)
??(?)
100mg100ml C1
100-90 /1000.1
10ml
11010mg
01
90-81 /900.1
90mg 100ml C0. 9
12
10ml
0.9109mg
81-72.9/810.1
81mg 100ml C0. 81
23
10ml
11010mg
72.9-65.6 /72.90.1
72.9mg100ml C0.72 9
10ml
11010mg
34