Fig. 6.

Zonation following dosing one ZoRLA with each of five compound having different potencies (k_a). For simplicity, pBypass for each SS and each compound was held constant at 0.8. At the start (t=0), a random p value was assigned to each SS_i. A dose of 50 compound was administered for each of 1000 simulation cycles. By then, stable patterns had emerged. A simulation cycle continued until all compound exited or were cleared. Values at early t during repeat experiments were not identical, but by t=1000 they became identical. X-axis: the distance from periportal edge to central vein exit was subdivided into ten regions. For each k_a experiment, there are four bar graphs. The two on the left provide measures of zonation. p_avg is the mean of all p_i's in one of the ten zones; p_i,t was updated using h=5. Using the default value h=70 used for Figs. 7–10, we were unable to clearly demonstrate the compound elimination shift effect. The clearance effort shift effect became more evident for smaller h values. We selected h=5 to demonstrate that peak compound elimination count can shift from PERIVENOUS to periportal as k_a increases. Clearance effort, p_avg, maps to average intrinsic clearance for a lobular tissue sample taken from the same relative location within a lobule. The cumulative total of compound eliminated by each SS_i was recorded. compound elimination count is the mean of those values for each region. On the right g is plotted, the value of the local gradient (which is the same for each of the five k_a experiments), and the mean, regional Q value.