Fig. 1.

Experimental design and dosing timeline. Rats assigned using block randomization (to ensure equal group membership) received either slow-IV infusion (referred to as IV) or IP injection for a specific terminal tissue collection (time frames indicated by circles along each experimental path). Black squares indicate start of experiment and induction of anesthesia. For IV study path (top line) the first black triangle indicates the start of infusion. The second black triangle indicates the completion (i.e. full dose delivered). For the IP study path (bottom line), the only triangle indicates the time at which full dose is delivered. For the short-term studies (grey box), all animals remain anesthetized until the specific terminal tissue collection time is reached (red circle). Four (4) animals were allocated to each red circle, for each of the two paths (IV and IP). Animals randomly assigned to the long-term study (white box), were removed from anesthesia (as detailed in Methods) following IV or IP dosing and allowed to survive for 72 h (4320 min) for terminal tissue collection (n = 4 per study path).