Dominant role for tissue binding in the first-pass extraction of imipramine by the perfused rat liver.
Dominant role for tissue binding in the first-pass extraction of imipramine by the perfused rat liver.
复制标题
组织结合在灌注大鼠肝脏首过提取丙咪嗪中起主导作用。
DOI：
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发表时间：
1977
期刊：
影响因子：
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通讯作者：
M. Bickel
中科院分区：
文献类型：
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作者：
R. Stegmann;M. Bickel
1. 在离体非循环大鼠肝脏制剂中灌注2分钟，研究丙咪嗪的动力学。2．在治疗范围 (5 × 10-6 M) 的流入浓度下，肝脏摄取为剂量的 99%，在 3 × 10-3 M 时降至 63%。摄取过程是饱和的，计算容量为 50 μmol/g 肝脏，但即使是灌注液中的最高浓度也远未达到饱和。实验过程中最大代谢率仅为1.1 μmol/g肝脏。在研究的浓度范围内，摄取率和代谢率的比率从 3.4 增加到 18。 Scatchard 对数据的评估揭示了两类结合位点，一类具有高亲和力/低容量，一类具有低亲和力/高容量。表观关联常数分别为 6 × 105 和 3 × 103 M-1。这种结合模式与体外膜组分的结合模式相当。3．将灌注速率从每克肝脏 4 毫升/分钟降低至 1 毫升/分钟并没有改变绝对上升...
1. The kinetics of imipramine were studied in the isolated non-recirculating rat liver preparation perfused for 2 min.2. At an influx concentration in the therapeutic range (5 × 10-6 M), hepatic uptake was 99% of the dose and decreased to 63% at 3 × 10-3 M. The uptake process was saturable and had a calculated capacity of 50 μmol/g liver, but even the highest concentrations in the perfusate were far from reaching saturation. Maximum metabolic rate was only 1.1 μmol/g liver during the experiment. The ratios of the rates of uptake and of metabolism increased from 3.4 to 18 over the concentration range studied. Scatchard evaluation of the data disclosed two classes of binding sites, one with high affinity /low capacity and one with low affinity/high capacity. The apparent association constants were 6 × 105 and 3 × 103 M-1 respectively. This binding pattern was comparable with that found with membrane fractions in vitro.3. Decreasing the perfusion rate from 4 to 1 ml/min per g liver did not alter absolute upt...