Cooper M R, Lieberman R, La Rocca R V, Gernt P R, Weinberger M S, Headlee D J, Kohler D R, Goldspiel B R, Peck C C, Myers C E
Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Clin Pharmacol Ther. 1992 Jul;52(1):11-23. doi: 10.1038/clpt.1992.97.
Suramin, a drug used in the treatment of parasitic diseases, is currently being evaluated in clinical trials as an antineoplastic agent. The use of therapeutic drug monitoring and adaptive control with feedback in clinical trials of suramin was initially motivated by an association between acute neurologic toxicity and plasma suramin concentrations in excess of 350 micrograms/ml. We have prospectively examined the performance of both two- and three-compartment population pharmacokinetic models in controlling plasma suramin concentrations and have found that a three-compartment model best describes this drug. No correlation was found between the clearance of suramin and creatinine clearance, as had been previously hypothesized. The low systemic clearance of suramin and the number of parameters required to describe the three-compartment model suggest the need for a bayesian approach to the estimation of individual pharmacokinetics.
苏拉明是一种用于治疗寄生虫病的药物，目前正在作为一种抗肿瘤药物进行临床试验评估。在苏拉明的临床试验中，使用治疗药物监测和反馈式自适应控制最初是由于急性神经毒性与血浆苏拉明浓度超过350微克/毫升之间的关联。我们前瞻性地研究了二室和三室群体药代动力学模型在控制血浆苏拉明浓度方面的性能，发现三室模型能最好地描述这种药物。如之前所假设的，未发现苏拉明清除率与肌酐清除率之间存在相关性。苏拉明较低的全身清除率以及描述三室模型所需的参数数量表明需要采用贝叶斯方法来估计个体药代动力学。
