Table 7. Oral Exposure and In Vivo Efficacy of Selected Compounds in an L. infantum Hamster Model of VL Following BID Dosing for 5 and 10 Daysa.
| reduction
in parasite burden, % |
||||||||
|---|---|---|---|---|---|---|---|---|
| liver |
spleen |
bone
marrow |
||||||
| compound | dose (mg/kg), BID | 5 days | 10 days | 5 days | 10 days | 5 days | 10 days | AUC0–24 after single p.o. dose of 50 mg/kg (h.ng/mL) |
| 5 | 25 | 89.7 | n.d. | 90.0 | n.d. | 77.0 | n.d. | 21 000 |
| 50 | 99.7 | n.d. | 99.2 | n.d. | 98.0 | n.d. | ||
| 16 | 25 | 87.8 | n.d. | 87.7 | n.d. | 72.2 | n.d. | 7900* |
| 50 | 99.6 | n.d. | 98.5 | n.d. | 95.1 | n.d. | ||
| 23 | 25 | 98.3 | 100 | 98.2 | 99.9 | 93.6 | 99.4 | 120 000 |
| 50 | 99.8 | n.d. | 99.9 | n.d. | 99.0 | n.d. | ||
| 28 | 25 | 98.9 | 99.4 | 97.8 | 96.9 | 95.7 | 84 | 21 000 |
| 50 | 99.9 | n.d. | 99.9 | n.d. | 99.1 | n.d. | ||
| 31 | 25 | 67.3 | n.d. | 69.0 | n.d. | 55.0 | n.d. | 21 000 |
| 50 | 99.4 | n.d. | 99.4 | n.d. | 99.7 | n.d. | ||
a
n = 6 animals per group, the results are expressed as a percentage reduction in amastigote burden compared to vehicle-treated, infected control animals, *Study run using a single 25 mg/kg p.o. dose.