Table 1.
In vivo efficacy models for cutaneous leishmaniasis drug discovery*
| Animal model (infected base tail) | Parasite | Initial drug dose schedule | Drug dose | Duration of therapy | Route and drug doses/week | Endpoint evaluated (day after infection) | Mean lesion size in negative controls, mm2 | Lesion size in positive controls, mm2 | % Suppression by positive control drug† |
|---|---|---|---|---|---|---|---|---|---|
| Tier 1a | |||||||||
| Mouse suppression: BALB/c mouse | L.m., L.p. | 3 days after infection | No prior in vivo: 40 MKD/160 MKD. Prior in vivo: ¼ LD50 | 1 qd × 10 d | IP = 22 | 28 (L.m.) 35 (L.p.) | 109 | AMB (25 MKD) IP = 8 | 93 |
| Tier 1b | |||||||||
| Mouse treatment: BALB/c mouse | L.m., L.p. | Lesion size = 2 mm in one dimension | Dose successful in mouse suppression test | 1 qd × 10 d | IP = 22 | 45 | 194 | AMB (25 MKD) IP = 8 | 92 |
| Tier 2 | |||||||||
| Mouse treatment: BALB/c mouse, PO drug | L.m., L.p. | Lesion size = 2 mm in one dimension | 1× and 4× dose successful in mouse treatment test with IP drug | 1 qd × 10 d | PO = 22 | 45 | 194 | AMB (25 MKD) IP = 8 | 92 |
| Tier 3 | |||||||||
| Hamster treatment: golden hamster, PO drug | L.p. | Lesion size = 70 mm2 | Full range of doses | 1 bid × 4 d | PO = 10 | 30 | 130 | Gluc (208 MKD) IM = 30 | 77 |
*
L.m. = Leishmania major; L.p. = L panamensis; MKD = mg/kg/day; LD50 = 50% lethal dose; qd = four times/day; d = day; IP = intraperitoneal; AMB = AmBiosome; PO = per os; Gluc = Glucantime; bid = two times/day.
†
% Suppression = 100 × [(negative control size − positive control size)/negative control size].