Meineke I, Schmidt W, Nottrott M, Schröder T, Hellige G, Gundert-Remy U
Department of Clinical Pharmacology, University of Göttingen, Germany.
Pharmacol Toxicol. 1997 Jun;80(6):266-71. doi: 10.1111/j.1600-0773.1997.tb01972.x.
Imipramine was administered to sheep (n = 10) by intravenous infusion in high doses (450 mg-900 mg) to elicit cardiovascular shock. A cardiac assist device was then employed to manage the acute overdose situation. The concentration-time course of imipramine and its metabolite desmethylimipramine in plasma was measured by HPLC. As an indicator of imipramine's cardiotoxic effect, cardiac output was monitored. The aim of the study was to evaluate the pharmacokinetics under these conditions and to assess the efficiency of a cardiac assist device with (n = 5) and without (n = 5) an integrated haemoperfusion unit in removing drug from the circulation. The kinetics of imipramine could be described by a three compartment body model with concentration-dependent clearance resulting in non-linear kinetics. The changes in cardiac output with time could be linked to the pharmacokinetic model by a linear relationship. The cardiac assist device was found to contribute to the overall elimination of imipramine whereas the haemoperfusion unit had no clinically relevant impact.
以高剂量（450毫克 - 900毫克）通过静脉输注向绵羊（n = 10）给予丙咪嗪以引发心血管休克。然后使用心脏辅助装置来处理急性过量用药情况。通过高效液相色谱法测定血浆中丙咪嗪及其代谢产物去甲丙咪嗪的浓度 - 时间过程。作为丙咪嗪心脏毒性作用的指标，监测心输出量。该研究的目的是评估在这些条件下的药代动力学，并评估带有（n = 5）和不带有（n = 5）集成血液灌注单元的心脏辅助装置从循环中清除药物的效率。丙咪嗪的动力学可以用三室体内模型来描述，其清除率取决于浓度，导致非线性动力学。心输出量随时间的变化可以通过线性关系与药代动力学模型相关联。发现心脏辅助装置有助于丙咪嗪的总体清除，而血液灌注单元没有临床相关影响。
