TABLE 1.

In vitro inhibitory activity of dual and triple combinations of DAPD TP, FTC TP, and l-FMAU TP on the RT activity of the wild-type DHBV polymerase^a

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

^aResults 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.