Figure 3.

Efficacy in adult interferon γ knockout mice with dosing starting on day 6 after infection. In all mice, the nanoluciferase-expressing Cryptosporidium parvum infectious dose was 1000 oocysts. A, Efficacy plots of bumped-kinase inhibitors (BKIs) 1294, 1369, 1534, and 1649 used for treatment of highly established infection when administered orally at 60 mg/kg once daily for 5 days. BKI 1649 was administered at 6 mg/kg once daily. All BKIs showed significant decreases in infection. B, Efficacy of subcutaneous versus oral dosing of mice with 1294 at 60 mg/kg, starting on day 6 after infection, for 5 days. BKI 1294 showed a significantly greater reduction in oocyst excretion when delivered orally as compared to an equivalent dose delivered subcutaneously (P < .05). This is probably due to a fecal concentration of orally administered 1294 that was higher than the 50% effective concentration (EC₅₀) early in the treatment period and to the longer presence of the orally administered 1294 in the lumen relative to the subcutaneously administered dose, for which the level after a single dose was below the EC₅₀. C, Efficacy of subcutaneous versus oral dosing with 1534 at 60 mg/kg, starting on day 6 after infection, for 5 days. No significant difference was seen in parasite excretion between the groups receiving the BKI doses.