Effect of altered tissue binding on the disposition of barbital in the isolated perfused rat liver: Application of the axial dispersion model

Chen Hsi Chou, Malcolm Rowland

研究成果: Article同行評審

10 引文 斯高帕斯(Scopus)

摘要

To examine the dependence of hepatic dispersion on tissue binding, the distribution kinetics of barbital under varying conditions of barbiturate perfusate concentrations was studied in the isolated perfused rat liver preparation (n = 5). The in situ liver was perfused in a single-pass mode with protein-free Krebs bicarbonate medium (15 mL/min). During steady-state infusion with various barbiturate concentrations (barbital, 1 g/L; butethal, 0.1, 1 g/L), a bolus containing [3H]water (cellular space marker) and [14C]barbital was injected into the portal vein. The recoveries of [3H]water and [14C]barbital were complete. The mean transit time and hence the volume of distribution for barbital in the absence of bulk barbiturate concentration (56 s and 1.24 mL/g) were about 2-fold higher than those for water (29 s and 0.58 mL/g), and they decreased progressly as the perfusate barbiturate concentration increased, indicating a decrease in tissue binding. However, the relative dispersion values (CV2(H)) of water (0.60) and barbital (0.66) were about the same magnitude and independent of the bulk concentration of barbiturate. The one-compartment dispersion model adequately described the data of barbital with a constant D(N) (dispersion number) value of 0.35. The results indicate that varying the tissue binding of barbital does not change the magnitude of D(N); as such it offers a new experimental approach to examine the hepatic dispersion of solutes with a large distribution volume.

原文English
頁(從 - 到)1310-1314
頁數5
期刊Journal of Pharmaceutical Sciences
86
發行號11
DOIs
出版狀態Published - 1997 11月

All Science Journal Classification (ASJC) codes

  • 藥學科學

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