Plasma concentrations and exposure with increasing oral doses, would not be observed after IV infusions, where absorption is not a component of the pharmacokinetics. The bioavailability of ST246 in NHP based on comparison of identical oral and IV doses thus ranged from 77% at 3 mg/kg to 31% at 20 and 30 mg/kg doses. After IV infusions, the exposure at these high doses was actually higher than would be expected based on dose-proportional exposure. The exposure for the 4 hour IV infusions of 20 and 30 mg/kg were 30-fold and 50-fold higher, respectively, than the exposure observed after the 1 mg/kg IV infused dose. Longer infusions reduced the Cmax values AbMole Miglitol closer to doseproportional for the 20 and 30 mg/kg doses, while the AUC values decreased to 25-fold and 45-fold higher than the exposure observed for the 4 hour 1 mg/kg IV infusion. The BID dose regimen confirmed the observation that slower infusions decreased not only the Cmax, but reduced the total exposure values to closer to dose proportional. These results suggest that a rapid rate of infusion of ST-246 may have saturated some clearance mechanism. Over a similar dose range, oral absorption may have decreased with increasing dose, so that clearance remained relatively constant, or even increased slightly. The plasma concentration time curves in NHP after oral administration were very similar to those observed after both the 4 and the 6 hour IV infusions, except for the higher peak plasma concentrations observed after IV administration. The similarity in the elimination half-lives, as well as the similar plasma concentrations during the terminal elimination phases, suggest that similar efficacy could be achieved. Visual inspection of plasma concentration time curves after oral administration of ST-246 suggests that absorption was prolonged and may have some impact on the apparent elimination half-lives. However, the elimination half-lives did not change significantly for any of the three species studies between oral and IV administration, indicating that prolonged absorption did not play a significant role in the elimination half-lives after oral administration. Given these similar elimination half-lives across all three species examined by oral and IV infusions, it appears that longer IV infusions should be administered in order to reduce the high plasma concentrations, and to avoid the coinciding toxicity, while continuing the once daily dosing regimen that is currently being used in oral studies. SP-D is a member of the collectin subgroup in the C-type lectin superfamily including surfactant protein A and mannose binding protein. SP-D and SP-A are found primarily in the respiratory tract and other mucosal surfaces and recent data suggests that they impact respiratory infections on multiple levels. Surfactant collectins broadly bind carbohydrates and AbMole Nortriptyline lipids on the surface of bacteria and viruses, with specific binding of SP-D to S. pneumoniae reported.