
3 курс / Фармакология / Диссертация_Ромодановский_Д_П_Разработка_требований_для_оценки_фармакокинетики
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385

ПРИЛОЖЕНИЯ
Приложение 1 – Общие сведения по дизайну исследований биоэквивалентности воспроизведенных препаратов
№ |
Дизайн |
Доза, мг |
Временные точки |
|
Период |
Количество |
Аналитически |
НПКО* |
НПКО*, |
|
|
|
|
|
отмывки |
субъектов |
й метод |
|
метаболита |
|
|
|
аторвастатин |
|
|
|
|
||
|
|
|
|
|
|
|
|
|
|
1 |
2х2х2 |
20 |
0.25, 0.5, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, 12, |
|
НД |
40 |
ВЭЖХ МС/МС |
0,5 |
0,5 |
|
|
|
24, 36, 48, 72 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
2 |
2х2х2 |
20 |
0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 8, 12, 16, 24 |
|
7 дней |
24 |
ВЭЖХ МС |
10 |
НД |
|
|
|
|
|
|
|
|
|
|
3 |
2х2х2 |
20 |
0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 |
|
НД |
18 |
НД |
НД |
НД |
|
|
|
|
|
|
|
|
|
|
4 |
2х2х2 |
80 |
0.25, 0.5, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, 12, |
|
7 дней |
46 |
ВЭЖХ МС/МС |
0,1 |
0,2 |
|
|
|
16, 24, 36, 48, 72 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
5 |
2х2х2 |
40 |
0, 0.167, 0.333, 0.5, 0.75, 1, 1.33, 1.67, 2, 3, 4, 6, |
|
14 дней |
54 |
ВЭЖХ МС/МС |
0,225 |
0,175 |
|
|
|
8, 16, 24, 30, 36, 48, 60 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
6 |
2х2х2 |
20 |
0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72 |
|
7 дней |
18 |
ВЭЖХ МС |
1 |
НД |
|
|
|
|
|
|
|
|
|
|
7 |
2х2х2 |
70 |
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 |
|
7 дней |
24 |
ВЭЖХ МС/МС |
10 |
НД |
|
|
|
|
|
|
|
|
|
|
8 |
2х2х2 |
40 |
0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 16, |
|
14 дней |
30 |
ВЭЖХ МС/МС |
0,225 |
0,175 |
|
|
|
24, 36, 48, 60, 72 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
9 |
2х2х2 |
40 |
0, 0.167, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, |
|
14 дней |
66 |
ВЭЖХ МС/МС |
0,225 |
0,177 |
|
|
|
3, 4, 6, 8, 12, 16, 24, 30, 36, 48, 60 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
10 |
2х2х2 |
20 |
0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 |
|
НД |
24 |
ВЭЖХ МС |
НД |
НД |
|
|
|
|
|
|
|
|
|
|
11 |
2х2х2 |
80 |
0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, |
|
7 дней |
77 |
ВЭЖХ МС/МС |
0,25 |
НД |
|
|
|
4.5, 5, 6, 8, 12, 24, 36, 48 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
12 |
2х2х2 |
40 |
0.5, 1, 1.5, 2, 3, 4, 6, 9, 24, 48 |
|
7 дней |
18 |
ВЭЖХ МС |
0,1 |
НД |
|
|
|
|
|
|
|
|
|
|
13 |
2х2х2 |
20 |
0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 |
|
7 дней |
18 |
ВЭЖХ МС |
1 |
НД |
|
|
|
|
|
|
|
|
|
|
14 |
2х2х2 |
40 |
0.2, 0.4, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48 |
|
30 дней |
24 |
ВЭЖХ МС/МС |
НД |
НД |
|
|
|
|
|
|
|
|
|
|
15 |
2х2х2 |
80 |
0, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 16, 24, |
|
14 дней |
42 |
ВЭЖХ МС/МС |
0,5 |
НД |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
386 |
|
|
|
|
№ |
Дизайн |
Доза, мг |
Временные точки |
|
Период |
Количество |
Аналитически |
НПКО* |
НПКО*, |
|
|
|
|
|
отмывки |
субъектов |
й метод |
|
метаболита |
|
|
|
36, 48, 60 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
16 |
2х2х2 |
20 |
0.5, 1, 1.5, 2, 3, 4, 6, 9, 24, 48 |
|
7 дней |
18 |
ВЭЖХ МС/МС |
5 |
НД |
|
|
|
|
|
|
|
|
|
|
17 |
2х2х2 |
20 |
0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 24, 48 |
|
7 дней |
18 |
ВЭЖХ МС/МС |
1 |
НД |
|
|
|
|
|
|
|
|
|
|
18 |
2х2х2 |
80 |
0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, |
|
14 дней |
44 |
ВЭЖХ МС/МС |
НД |
НД |
|
|
|
6, 8, 12, 24, 36, 48, 72, 96, 120 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
19 |
2х2х2 |
20 |
0, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 18, |
|
14 дней |
26 |
ВЭЖХ МС/МС |
0,1 |
НД |
|
|
|
24, 48, 72 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
20 |
2х2х2 |
80 |
0.5, 1, 2, 3, 4, 5, 7, 10, 24, 48, 80 |
|
14 дней |
18 |
ВЭЖХ МС |
0,3 |
НД |
|
|
|
|
|
|
|
|
|
|
21 |
2х2х2 |
40 |
0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60 |
|
7 дней |
18 |
ВЭЖХ МС |
1 |
НД |
|
|
|
|
|
|
|
|
|
|
22 |
2х2х2 |
20 |
0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 48 |
|
7 дней |
24 |
ВЭЖХ МС |
0,25 |
НД |
|
|
|
|
|
|
|
|
|
|
23 |
2х2х2 |
40 |
0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, |
|
7 дней |
18 |
ВЭЖХ МС |
50 |
НД |
|
|
|
36, 48, 60 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
24 |
2х2х2 |
80 |
0, 0.17, 0.5, 1, 1.5, 2, 3, 4, 5, 7, 10, 24, 48, 72 |
|
7 дней |
18 |
ВЭЖХ МС |
1 |
НД |
|
|
|
|
|
|
|
|
|
|
25 |
2х2х2 |
40 |
0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 48 |
|
7 дней |
24 |
ВЭЖХ МС |
0,25 |
НД |
|
|
|
|
|
|
|
|
|
|
26 |
2х2х2 |
80 |
0, 0.25, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 12, 24, 48, 72 |
|
7 дней |
18 |
ВЭЖХ МС |
1 |
НД |
|
|
|
|
|
|
|
|
|
|
27 |
2х2х2 |
80 |
0.5, 1, 1.5, 2, 3, 4, 5, 7, 10, 24, 48 |
|
14 дней |
24 |
ВЭЖХ МС/МС |
0,2 |
НД |
|
|
|
|
|
|
|
|
|
|
28 |
2х2х2 |
80 |
0, 0.167, 0.5, 1, 1.5, 2, 3, 4, 5, 7, 10, 24, 48, 72 |
|
7 дней |
44 |
ВЭЖХ МС |
1 |
1 |
|
|
|
|
|
|
|
|
|
|
29 |
2х2х2 |
80 |
0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, |
|
14 дней |
41 |
ВЭЖХ МС/МС |
0,1 |
НД |
|
|
|
16, 24, 36, 48, 72 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
30 |
2х2х2 |
40 |
0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, |
|
7 дней |
18 |
ВЭЖХ МС |
0,3 |
НД |
|
|
|
60 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
31 |
2х2х2 |
80 |
0, 0.25, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 12, 24, 48, 72 |
|
7 дней |
18 |
ВЭЖХ МС |
1 |
НД |
|
|
|
|
|
|
|
|
|
|
32 |
2х2х2 |
80 |
0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 |
|
14 дней |
24 |
ВЭЖХ УФ |
500 |
НД |
|
|
|
|
|
|
|
|
|
|
33 |
2х2х2 |
40 |
0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 48, 72 |
|
7 дней |
42 |
ВЭЖХ МС |
0,5 |
НД |
|
|
|
|
|
|
|
|
|
|
34 |
2х2х2 |
80 |
0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 48, 72 |
|
14 дней |
28 |
ВЭЖХ МС/МС |
1 |
1 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
387 |
|
|
|
|

№ |
Дизайн |
Доза, мг |
Временные точки |
|
Период |
Количество |
Аналитически |
НПКО* |
НПКО*, |
|
|
|
|
|
отмывки |
субъектов |
й метод |
|
метаболита |
|
|
|
симвастатин |
|
|
|
|
||
|
|
|
|
|
|
|
|
|
|
1 |
2х2х2 |
40 |
0, 1, 2, 3, 4, 5, 6, 9, 12, 24 |
|
7 дней |
12 |
ВЭЖХ МС |
0,6 |
НД |
|
|
|
|
|
|
|
|
|
|
2 |
2х2х2 |
40 |
0, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, |
|
7 дней |
36 |
ВЭЖХ МС |
0,1 |
0,5 |
|
|
|
14 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
3 |
2х2х2 |
80 |
1, 1.5, 2, 3, 4, 5, 6, 8, 10 |
|
7 дней |
18 |
ВЭЖХ УФ |
НД |
10 |
|
|
|
|
|
|
|
|
|
|
4 |
2х2х2 |
80 |
1, 1.5, 2, 3, 4, 5, 6, 8, 10 |
|
7 дней |
18 |
ВЭЖХ УФ |
НД |
10 |
|
|
|
|
|
|
|
|
|
|
5 |
2х2х2 |
80 |
1, 1.5, 2, 3, 4, 5, 6, 8, 10 |
|
7 дней |
18 |
ВЭЖХ УФ |
НД |
10 |
|
|
|
|
|
|
|
|
|
|
6 |
2х2х2 |
40 |
0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, |
|
24 дня |
47 |
ВЭЖХ МС |
0,15 |
0,15 |
|
|
|
14, 16, 24 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
7 |
2х2х2 |
20 |
0, 0.25, 0.5, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, |
|
14 дней |
24 |
ВЭЖХ МС |
0,2 |
0,2 |
|
|
|
12, 24 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
8 |
2х2х2 |
40 |
0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 |
|
7 дней |
18 |
ВЭЖХ МС |
0,2 |
0,1 |
|
|
|
|
|
|
|
|
|
|
9 |
2х2х2 |
40 |
0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 |
|
7 дней |
18 |
ВЭЖХ МС |
0,2 |
0,1 |
|
|
|
|
|
|
|
|
|
|
10 |
2х2х2 |
40 |
0, 0.25, 0.5, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, |
|
24 дня |
24 |
ВЭЖХ МС/МС |
0,2 |
0,2 |
|
|
|
12, 24 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
11 |
2х2х2 |
40 |
0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 20, |
|
14 дней |
36 |
ВЭЖХ МС/МС |
0,2 |
0,2 |
|
|
|
24, 30, 36 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
12 |
2х2х2 |
40 |
0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24 |
|
7 дней |
18 |
ВЭЖХ МС |
НД |
0,05 |
|
|
|
|
|
|
|
|
|
|
13 |
2х2х2 |
40 |
0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24 |
|
7 дней |
18 |
ВЭЖХ МС |
НД |
0,05 |
|
|
|
|
|
|
|
|
|
|
14 |
2х2х2 |
80 |
0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 |
|
14 дней |
31 |
ВЭЖХ МС |
0,2 |
НД |
|
|
|
|
|
|
|
|
|
|
15 |
2х2х2 |
40 |
0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24 |
|
7 дней |
18 |
ВЭЖХ МС |
НД |
0,05 |
|
|
|
|
|
|
|
|
|
|
16 |
2х2х2 |
20 |
0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24 |
|
7 дней |
18 |
ВЭЖХ УФ |
0,1 |
0,1 |
|
|
|
|
|
|
|
|
|
|
17 |
2х2х2 |
80 |
0, 0.33, 0.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.5, 4, |
|
8 дней |
60 |
ВЭЖХ МС |
0,76 |
0,38 |
|
|
|
6, 8, 10, 12, 24 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
18 |
2х2х2 |
40 |
0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, |
|
10 дней |
21 |
ВЭЖХ МС/МС |
0,4 |
0,36 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
388 |
|
|
|
|
№ |
Дизайн |
Доза, мг |
Временные точки |
|
Период |
Количество |
Аналитически |
НПКО* |
НПКО*, |
|
|
|
|
|
отмывки |
субъектов |
й метод |
|
метаболита |
|
|
|
3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
19 |
2х2х2 |
40 |
0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, |
|
14 дней |
63 |
ВЭЖХ МС/МС |
0,2 |
НД |
|
|
|
4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
розувастатин |
|
|
|
|
||
|
|
|
|
|
|
|
|
|
|
1 |
2×2×2 |
40 |
1; 1,5; 2; 2,5; 3; 3,5; 4; 4,5; 5; 5,5; 6; 7; 8; 9; 12; |
|
14 дней |
39 |
ВЭЖХ МС/МС |
НД |
|
|
|
|
16; 24; 36; 48; 72; 96 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
2 |
2×2×2 |
20 |
0,5; 1; 1,5; 2; 2,5; 3; 4; 6; 12; 24; 36; 48; 72 |
|
14 дней |
18 |
ВЭЖХ МС |
0,2 |
|
|
|
||||||||
|
|
|
|
|
|
|
|
|
|
3 |
2×2×2 |
20 |
0,5; 1; 1,5; 2; 2,5; 3; 4; 6; 12; 24; 36; 48; 73 |
|
14 дней |
18 |
ВЭЖХ МС |
0,2 |
|
|
|
|
|
|
|
|
|
|
|
4 |
2×2×2 |
40 |
0,5; 1; 1,5; 2; 2,5; 3; 3,5; 4; 4,2; 4,4; 5; 5,2; 5,4; 6; |
|
14 дней |
24 |
ВЭЖХ МС |
0,1 |
|
|
|
|
8; 12; 24; 36; 48; 72 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
5 |
2×2×2 |
40 |
0,5; 1; 1,5; 2; 2,5; 3; 3,5; 4; 5; 6; 8; 10; 12; 24; 48; |
|
10 дней |
24 |
ВЭЖХ МС |
1 |
|
|
|
|
80 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
6 |
2×2×2 |
20 |
1; 2; 3; 4; 5; 6; 8; 12; 24; 48; 72 |
|
14 дней |
24 |
ВЭЖХ МС |
2 |
|
|
|
|
|
|
|
|
|
|
|
7 |
2×2×2 |
20 |
0,75; 1,5; 2; 2,5; 3; 3,5; 4; 4,5; 5; 5,5; 6; 7; 8; 10; |
|
14 дней |
40 |
ВЭЖХ МС/МС |
0,5 |
|
|
|
||||||||
|
|
|
14; 24; 36; 48; 72; 96 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
8 |
2×2×2 |
20 |
1; 2; 3; 4; 5; 6; 8; 12; 24; 48; 72 |
|
14 дней |
18 |
ВЭЖХ МС |
0,5 |
|
|
|
|
|
|
|
|
|
|
|
9 |
2×2×2 |
40 |
1; 3; 4; 5; 6; 7; 8; 10; 24; 48; 72 |
|
14 дней |
24 |
ВЭЖХ МС/МС |
0,5 |
|
|
|
|
|
|
|
|
|
|
|
10 |
2×2×2 |
20 |
1; 2; 3; 4; 5; 6; 7; 8; 10; 12; 24; 48; 72 |
|
14 дней |
24 |
ВЭЖХ МС/МС |
1,5 |
|
|
|
|
|
|
|
|
|
|
|
11 |
2×2×2 |
40 |
1; 2; 3; 4; 5; 6; 8; 12; 24; 48; 72 |
|
14 дней |
34 |
ВЭЖХ МС/МС |
0,1 |
|
|
|
|
|
|
|
|
|
|
|
12 |
2×2×2 |
40 |
1; 2; 3; 4; 5; 6; 8; 12; 24; 48; 72 |
|
14 дней |
28 |
ВЭЖХ МС |
1,5 |
|
|
|
||||||||
|
|
|
|
|
|
|
|
|
|
13 |
2×2×2 |
20 |
1; 2; 3; 4; 5; 6; 8; 12; 24; 48; 72 |
|
14 дней |
28 |
ВЭЖХ МС |
1,5 |
|
|
|
|
|
|
|
|
|
|
|
14 |
2×2×2 |
20 |
1; 2; 3; 4; 5; 6; 8; 12; 24; 48; 72 |
|
14 дней |
28 |
ВЭЖХ МС/МС |
0,25 |
|
|
|
||||||||
|
|
|
|
|
|
|
|
|
|
15 |
2×2×2 |
20 |
1; 2; 3; 4; 5; 6; 7; 8; 10; 16; 24; 36; 48; 72 |
|
14 дней |
36 |
ВЭЖХ МС/МС |
0,2 |
|
|
|
||||||||
|
|
|
|
|
|
|
|
|
|
16 |
2×2×2 |
20 |
1; 2; 3; 4; 5; 6; 7; 8; 10; 24; 48; 72 |
|
14 дней |
28 |
ВЭЖХ МС/МС |
1 |
|
|
|
|
|
|
|
|
|
|
|
17 |
2×2×2 |
20 |
0,33; 0,67; 1; 1,5; 2; 2,5; 3; 3,33; 3,67; 4; 4,33; |
|
7 дней |
36 |
ВЭЖХ МС/МС |
0,2 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
389 |
|
|
|
|

№ |
Дизайн |
Доза, мг |
Временные точки |
|
Период |
Количество |
Аналитически |
НПКО* |
НПКО*, |
|
|
|
|
|
|
отмывки |
субъектов |
й метод |
|
|
метаболита |
|
|
|
4,67; 5; 5,33; 5,67; 6; 8; 10; 12; 24; 48; 72 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
18 |
2×2×2 |
40 |
0; 1; 2; 3; 4; 4,5; 5; 5,5; 6; 7; 8; 9; 10; 12; 24; 48; |
|
14 дней |
24 |
ВЭЖХ МС/МС |
0,5 |
|
|
|
|
|
72 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
ловастатин |
|
|
|
|
|
||
|
|
|
|
|
|
|
|
|
|
|
1 |
2х2х2 |
80 |
0.5, 1, 1.5, 2, 4, 6, 8, 10, 12 |
|
7 дней |
18 |
ВЭЖХ УФ |
|
|
10 нг/мл |
|
|
|
|
|
|
|
|
|
|
|
2 |
2х2х2 |
40 |
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 14, 20, 24, 26, |
|
14 дней |
40 |
ВЭЖХ МС/МС |
НД |
НД |
|
|
|
|
30, 34, 38, 48 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
3 |
2х2х2 |
40 |
0, 0.5, 1, 1.5, 2, 2.5, 3, 6, 10, 24 |
|
7 дней |
18 |
ВЭЖХ МС |
1 нг/мл |
1 нг/мл |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
каптоприл |
|
|
|
|
|
||
|
|
|
|
|
|
|
|
|
|
|
1 |
2х2х2 |
50 |
0; 0,25; 0,5; 0,75; 1; 1,5; 2; 2,5; 3; 4; 6 |
|
7 |
12 |
ВЭЖХ УФ |
10 |
|
|
|
|
|
|
|
|
|
|
|
|
|
2 |
2х2х2 |
50 |
0; 0,25; 0,5; 0,75; 1; 1,5; 2; 3; 3,5; 4; 5 |
|
7 |
18 |
ВЭЖХ МС |
20 |
|
|
|
|
|
||||||||
|
|
|
|
|
|
|
|
|
|
|
3 |
2х2х2 |
50 |
0; 0,5; 1; 1,5; 2; 4; 6; 8 |
|
7 |
18 |
ВЭЖХ МС |
30 |
|
|
|
|
|
|
|
|
|
|
|
|
|
4 |
2х2х2 |
50 |
0; 0,25; 0,5; 1; 1,5; 2; 3; 4; 5; 8; 12 |
|
7 |
18 |
ВЭЖХ МС |
7 |
|
|
|
|
|
|
|
|
|
|
|
|
|
5 |
2х2х2 |
25 |
0; 0,15; 0,33; 0,75; 1; 1,5; 2; 3; 4; 6; 8 |
|
7 |
12 |
ВЭЖХ МС |
5 |
|
|
|
|
|
||||||||
|
|
|
|
|
|
|
|
|
|
|
6 |
2х2х2 |
50 |
0; 0,17; 0,33; 0,5; 0,75; 1; 1,5; 2; 3; 4; 6; 8 |
|
7 |
18 |
ВЭЖХ УФ |
15 |
|
|
|
|
|
||||||||
|
|
|
|
|
|
|
|
|
|
|
7 |
2х2х2 |
25 |
0; 0,25; 0,5; 1; 1,5; 2; 3; 4; 5; 8; 24 |
|
7 |
18 |
ВЭЖХ МС |
7 |
|
|
|
|
|
|
|
|
|
|
|
|
|
8 |
2х2х2 |
25 |
0; 0,25; 0,5; 1; 1,5; 2; 3; 4; 5; 8; 24 |
|
7 |
18 |
ВЭЖХ МС |
7 |
|
|
|
|
|
|
|
|
|
|
|
|
|
9 |
2х2х2 |
50 |
0; 0,25; 0,5; 0,75; 1; 1,5; 2; 2,5; 3; 4; 5 |
|
7 |
18 |
ВЭЖХ МС |
20 |
|
|
|
|
|
||||||||
|
|
|
|
|
|
|
|
|
|
|
10 |
2х2х2 |
50 |
0; 0,25; 0,5; 0,75; 1; 1,5; 2; 3; 3,5; 4; 5 |
|
7 |
18 |
ВЭЖХ УФ |
20 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
лизиноприл |
|
|
|
|
|
||
|
|
|
|
|
|
|
|
|
|
|
1 |
2х2х2 |
10 |
0; 1; 3; 5; 6; 7; 8; 9; 10; 24; 30; 48 |
|
14 |
18 |
ВЭЖХ МС |
1,0 |
|
|
|
|
|
|
|
|
|
|
|
|
|
2 |
2х2х2 |
10 |
0; 1; 2; 4; 6; 7; 7,5; 8; 10; 12; 18; 24; 36; 48 |
|
7 |
18 |
ВЭЖХ ФЛУ |
10,0 |
|
|
|
|
|
||||||||
|
|
|
|
|
|
|
|
|
|
|
3 |
2х2х2 |
20 |
0; 1; 2; 4; 6; 8; 10; 12; 14; 24; 48 |
|
14 |
24 |
РИА |
2,0 |
|
|
|
|
|
|
|
|
|
|
|
|
|
4 |
2х2х2 |
20 |
0; 1; 3; 5; 6; 7; 8; 9; 10; 24; 30; 48 |
|
14 |
18 |
ВЭЖХ МС |
1,0 |
|
|
|
|
|
|
|
|
|
|
|
|
|
5 |
2х2х2 |
20 |
0; 1; 2; 3; 4; 5; 5,5; 6; 6,5; 7; 7,5; 8; 9; 12; 16; 24; |
|
8 |
34 |
ВЭЖХ МС/МС |
1,3 |
|
|
|
|
|
30; 36; 48 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
390 |
|
|
|
|
|