Sutherland I A, Mounsey A, Eisler M, Holmes P H
Department of Veterinary Physiology, University of Glasgow Veterinary School, Scotland.
Parasitology. 1992 Aug;105 ( Pt 1):91-5. doi: 10.1017/s0031182000073728.
Clones of Trypanosoma congolense which express resistance to the widely used trypanocide isometamidium chloride accumulate less of the drug than clones which are sensitive to drug treatment. A mathematical model has been developed which was able to predict theoretical lines representing the uptake kinetics in trypanosomes which were sensitive to isometamidium, as well as for resistant trypanosomes in which reduced accumulation was a result of either reduced uptake or enhanced efflux of the drug. Data from drug uptake experiments were then fitted to these theoretical lines. While the value for drug efflux could not be separated from the dissociation constant of the trypanosomes for isometamidium, it was demonstrated that reduced accumulation is not a result of reduced uptake of isometamidium by drug-resistant trypanosomes.
对广泛使用的杀锥虫药氯异喹啉具有抗性的刚果锥虫克隆，与对药物治疗敏感的克隆相比，积累的药物更少。已开发出一个数学模型，该模型能够预测代表对氯异喹啉敏感的锥虫以及抗性锥虫摄取动力学的理论曲线，在抗性锥虫中，药物积累减少是药物摄取减少或药物外排增强的结果。然后将药物摄取实验的数据与这些理论曲线进行拟合。虽然药物外排的值无法与锥虫对氯异喹啉的解离常数区分开来，但已证明药物抗性锥虫积累减少不是由于氯异喹啉摄取减少所致。
