González-Martin G, Ponce G, Inostroza V, González M, Paulos C, Guevara A
Department of Pharmacy, Faculty of Chemistry, Pontifical Catholic University, Santiago, Chile.
J Pharm Pharmacol. 1993 Jan;45(1):72-4. doi: 10.1111/j.2042-7158.1993.tb03684.x.
The disposition of nifurtimox was studied in the rat isolated perfused liver using a recirculating system. The drug was administered as a bolus (5.0, 15.0 or 30.0 micrograms mL-1), and its disappearance was monitored by analysing perfusate samples. In all experiments perfusate disappearance was monoexponential, and no significant difference was found between the three doses for the elimination constant (0.016, 0.011 and 0.012 min-1, respectively), half-life (46.6, 65.8 and 66.8 min, respectively), extraction rate (0.128, 0.091 and 0.099, respectively) and distribution volume (41.1, 47.3 and 30.7 mL g-1, respectively). At 30 micrograms mL-1 the hepatic clearance was lower than the other concentrations of nifurtimox (0.66, 0.51 and 0.34 mL min-1 g-1, respectively). Relatively little parent drug was recovered from the liver at the end of the perfusions. In summary, nifurtimox is cleared slowly from the rat isolated perfused liver, is poorly extracted by hepatocyte cells and is completely metabolized from 2 to 4 h after perfusion.
采用循环系统，在大鼠离体灌注肝脏中研究了硝呋替莫的处置情况。该药物以大剂量（5.0、15.0或30.0微克/毫升）给药，并通过分析灌注液样本监测其消失情况。在所有实验中，灌注液的消失呈单指数形式，三种剂量之间的消除常数（分别为0.016、0.011和0.012分钟-1）、半衰期（分别为46.6、65.8和66.8分钟）、提取率（分别为0.128、0.091和0.099）和分布容积（分别为41.1、47.3和30.7毫升/克）均未发现显著差异。在30微克/毫升时，肝脏清除率低于其他浓度的硝呋替莫（分别为0.66、0.51和0.34毫升/分钟/克）。在灌注结束时，从肝脏中回收的母体药物相对较少。总之，硝呋替莫从大鼠离体灌注肝脏中清除缓慢，肝细胞对其提取较差，且在灌注后2至4小时完全代谢。
