Consideration on Moments of Outflow Profile in Liver Perfusion System with Change in Perfusate Flow Rate Using Oxacillin as Model Drug

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概要

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• 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 (F_H) 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 (σ^2/t^^^-^2_H) 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 σ^2/t^^^-^2_H 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 (F_H, t^^^-_H and σ^2/t^^^-^2_H) 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 (F_H>50%), i.e., F_H is independent of the distribution, both F_H and t^^^-_H are independent of the dispersion process in the hepatic blood space, and both t^^^-_H and σ^2/t^^^-^2_H are independent of the elimination. Thus, it is shown that F_H and t^^^-_H are exactly the indices of elimination and distribution, respectively, and σ^2/t^^^-^2_H is the index of dispersion in the blood space plus nonequilibrium in the hepatic distribution.

• 公益社団法人日本薬学会の論文
• 1996-01-15

著者

• Higashi Yutaka

  School Of Pharmacy Shujitsu University

• Nakagawa Terumichi

  Faculty Of Pharmaceutical Science Kyoto University

• Yamaoka Kiyoshi

  Faculty Of Pharmaceutical Science Kyoto University

• OHATA Yuka

  Faculty of Pharmaceutical Science, Kyoto University

• YASUI Hiroyuki

  Faculty of Pharmaceutical Science, Kyoto University

• Yasui Hiroyuki

  Faculty Of Pharmaceutical Science Kyoto University

• Ohata Yuka

  Faculty Of Pharmaceutical Science Kyoto University

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