TABLE 1.
Combination and concn (μM) | 2 radiolabeled nucleosides
|
3 radiolabeled nucleosides
|
||||
---|---|---|---|---|---|---|
Experimental inhibition (%) | Theoretical additivity | Bliss independence | Experimental inhibition (%) | Theoretical additivity | Bliss independence | |
DAPD-l-FMAU | ||||||
1, 10 | 29 ± 5 | 35 ± 11 | >Single | |||
1, 25 | 33 ± 4 | 36 ± 16 | >Single/ADD | 38 ± 7 | 51 ± 7 | >Single |
1, 50 | 34 ± 4 | 39 ± 13 | >Single/ADD | 50 ± 11 | 54 ± 9 | >Single/ADD |
1, 100 | 43 ± 6 | 45 ± 13 | >Single/ADD | 51 ± 16 | 60 ± 10 | >Single |
DAPD-FTC | ||||||
1, 1 | 42 ± 12 | 45 ± 11 | >Single/ADD | |||
1, 5 | 57 ± 6 | 56 ± 8 | ADD | |||
1, 10 | 56 ± 13 | 45 ± 16 | SYN | 44 ± 5 | 56 ± 5 | >Single |
1, 50 | 46 ± 10 | 65 ± 9 | >Single | |||
1, 100 | 66 ± 9 | 79 ± 10 | >Single | 50 ± 12 | 68 ± 7 | >Single |
FTC-l-FMAU | ||||||
1, 10 | 12 ± 10 | 24 ± 6 | >l-FMAU Single | |||
1, 50 | 34 ± 18 | 39 ± 1 | >Single/ADD | |||
1, 100 | 44 ± 8 | 49 ± 4 | >Single/ADD | |||
10, 10 | 37 ± 4 | 45 ± 0 | >Single | |||
10, 25 | 33 ± 14 | 44 ± 5 | >Single | |||
10, 50 | 43 ± 8 | 56 ± 4 | >Single | 36 ± 4 | 47 ± 6 | >Single |
10, 100 | 53 ± 4 | 63 ± 6 | >Single | 51 ± 13 | 54 ± 8 | >Single/ADD |
50, 25 | 40 ± 7 | 55 ± 11 | >l-FMAU Single | |||
50, 50 | 49 ± 8 | 57 ± 9 | >Single | |||
50, 100 | 49 ± 9 | 63 ± 11 | >Single | |||
100, 10 | 65 ± 5 | 74 ± 2 | >Single | |||
100, 25 | 44 ± 8 | 59 ± 7 | >l-FMAU Single | |||
100, 50 | 72 ± 3 | 79 ± 4 | >Single | 50 ± 4 | 61 ± 6 | >Single |
100, 100 | 71 ± 2 | 82 ± 4 | >Single | 66 ± 4 | 66 ± 8 | ADD |
DAPD-FTC-l-FMAU | ||||||
1, 10, 25 | 48 ± 11 | 65 ± 7 | >Double | |||
1, 10, 50 | 47 ± 8 | 67 ± 7 | >Double | |||
1, 10, 100 | 58 ± 5 | 71 ± 6 | >Double | |||
1, 50, 25 | 48 ± 4 | 72 ± 8 | >Double | |||
1, 50, 50 | 51 ± 8 | 74 ± 9 | >Double | |||
1, 50, 100 | 56 ± 4 | 77 ± 9 | >Double | |||
1, 100, 25 | 45 ± 6 | 75 ± 6 | <FTC Single | |||
1, 100, 50 | 50 ± 7 | 76 ± 6 | >Double | |||
1, 100, 100 | 61 ± 13 | 79 ± 7 | <l-FMAU + FTC |
Results are expressed as percentages of inhibition of viral minus-strand DNA elongation and correspond to the mean values of 4 experiments. Abbreviations: ADD, additivity; SYN, synergy; >Single or double, effect superior to single or double drug combination.