Abstract
The effect of perfusate flow rate on hepatic structure and hepatic uptake kinetics was investigated using oxacillin as a model drug and bovine serum albumin (BSA) as a reference substance in the liver perfusion system from the standpoint of a dispersion model and moment characteristics. The estimated recovery ratio (FH) of oxacillin was about 40% which was independent of the change in perfusate flow rate. The mean transit time (t^^-H) of oxacillin decreased with an increase in flow rate, while the relative variance (σ2/t^^-2H) of oxacillin was independent of the flow rate. The t^^-H of BSA decreased with an increase in the flow rate to the same extent as that of oxacillin, while σ2/t^^-2H of BSA was independent of flow rate. When the dispersion model is adopted as a model system to analyze hepatic perfusion data following the pulse input, the moment characteristics (FH, t^^-H and σ2/t^^-2H) are given in complicated equations. It is demonstrated by the present investigation that these moment equations can be extensively simplified for a drug with a medium extraction ratio (FH>50%), i.e., FH is independent of the distribution, both FH and t^^-H are independent of the dispersion process in the hepatic blood space, and both t^^-H and σ2/t^^-2H are independent of the elimination. Thus, it is shown that FH and t^^-H are exactly the indices of elimination and distribution, respectively, and σ2/t^^-2H is the index of dispersion in the blood space plus nonequilibrium in the hepatic distribution.
