TABLE 4.
Efficacy of E1224 in monotherapy or combined with benznidazole for 20 days in a Trypanosoma cruzi drug-resistant murine modela
| Time point | Exptl groupb | Parasitemia clearance, days (mean ± SD) | Parasitemia relapse, days (mean ± SD) | Patent parasitemia, days (mean ± SD) | Parasitemia AUC±SD (×103)c | No. of surviving/total (%)d | Total negative assays/total (%)e |
|---|---|---|---|---|---|---|---|
| 4th dpi | E1224 (50) | 1.22 ± 0.66 | 28.85 ± 3.98 | 29.10 ± 3.98 | 1,859 ± 1,345 | 9/9 (100) | 0/9 (0) |
| Bz (100) | 1 | 24.16 ± 10.88 | 22.16 ± 9.43 | 814 ± 1026 | 8/8 (100) | 2/8 (25) | |
| E1224 (50) + Bz (100) | 1 | ND | ND | 0 | 10/10 (100) | 10/10 (100) | |
| E1224 (37.5) | 1.22 ± 0.66 | 18.4 ± 3.75 | 26 ± 3.53 | 2,378 ± 3,452 | 7/7 (100) | 0/7 (0) | |
| Bz (75) | 1 | 18.33 ± 3.51 | 28 ± 3.60 | 489 ± 755 | 7/7 (100) | 0/7 (0) | |
| E1224 (37.5) + Bz (75) | 1 | 37.75 ± 7.36 | 13.25 ± 0.27 | 54 ± 124 | 10/10 (100) | 4/10 (40) | |
| 10th dpi | E1224 (50) | 5.85 ± 2.03 | 8.71 ± 3.30 | 36.71 ± 2.28 | 1,513 ± 869 | 7/7 (100) | 0/7 (0) |
| Bz (100) | 5.42 ± 2.87 | 28.14 ± 11.35 | 26.28 ± 7.52 | 530 ± 863 | 7/7 (100) | 0/7 (0) | |
| E1224 (50) + Bz (100) | 4.14 ± 2.41 | 27.57 ± 3.04 | 15.85 ± 5.52 | 53 ± 32 | 7/7 (100) | 0/7 (0) | |
| E1224 (37.5) | 6,66 ± 1.96 | 10.28 ± 1.11 | 36 ± 5.06 | 1,031 ± 622 | 7/7 (100) | 0/7 (0) | |
| Bz (75) | 5.57 ± 1.61 | 22.85 ± 4.52 | 24.14 ± 4.45 | 328 ± 525 | 7/7 (100) | 0/7 (0) | |
| E1224 (37.5) + Bz (75) | 4.0 ± 1.73 | 28.57 ± 4.85 | 16.71 ± 5.46 | 84 ± 101 | 7/7 (100) | 0/7 (0) | |
| Infected untreated | 43 ± 5.57 | ND | 43 ± 5.57 | 23,836 ± 12,317 | 4/15 (26.6) | 0/15 (0) |
a
Swiss female mice (7 to 10/group) weighing 20 to 24 g were inoculated with 5 × 103 trypomastigotes of the benznidazole-resistant Colombian strain.
b
Oral treatment was initiated on the 4th or 10th day postinoculation (dpi) and continued for 20 days. Numbers in parentheses are doses in milligrams per kilogram.
c
Area under the curve of parasitemia until 60 days after infection.
d
Survival until 30 days after treatment.
e
Negative fresh blood examination and negative PCR assay results performed during the 1st and 6th months after treatment.