Burri C, Onyango J D, Auma J E, Burudi E M, Brun R
Swiss Tropical Institute (STI), Basel.
Acta Trop. 1994 Oct;58(1):35-49. doi: 10.1016/0001-706x(94)90120-1.
The level of the trypanocidal drug melarsoprol was determined in serum and cerebrospinal fluid (CSF) of six healthy vervet monkeys after intravenous application of the drug following a standard treatment schedule and a recently suggested alternative protocol. The maximum serum levels measured were about 3 micrograms/ml. A three-compartment model was used to analyze the serum data. The mean residence time calculated for melarsoprol in serum was 18 h, the volume of distribution was 3.6 l/kg and the clearance was 3.5 ml/min*kg. In the CSF the drug levels were generally very low, not exceeding 55 ng/ml, and the adaptation of the drug levels was found to be very low. The comparison of the drug concentrations required to eliminate trypanosomes in vitro and the drug concentrations reached in the CSF during treatment revealed that the latter might be insufficient in some cases to eliminate all trypanosomes from this site. The peak serum levels during alternative application of the drug were lower compared to those during empirical treatment. No evidence for drug cumulation in the body was found. The results of this study are compared with recent pharmacokinetic data from human patients, and discussed in the context of the problem of relapses and reactive encephalopathy occurring after treatment of sleeping sickness.
在六只健康的绿猴按照标准治疗方案和最近建议的替代方案静脉注射杀锥虫药物美拉胂醇后，测定了血清和脑脊液（CSF）中美拉胂醇的水平。测得的最高血清水平约为3微克/毫升。采用三室模型分析血清数据。计算出美拉胂醇在血清中的平均驻留时间为18小时，分布容积为3.6升/千克，清除率为3.5毫升/分钟·千克。脑脊液中的药物水平通常非常低，不超过55纳克/毫升，且发现药物水平的适应性非常低。体外消除锥虫所需的药物浓度与治疗期间脑脊液中达到的药物浓度的比较表明，在某些情况下，后者可能不足以从该部位消除所有锥虫。与经验性治疗期间相比，药物替代应用期间的血清峰值水平较低。未发现体内药物蓄积的证据。将本研究结果与近期人类患者的药代动力学数据进行了比较，并在昏睡病治疗后出现复发和反应性脑病问题的背景下进行了讨论。
