Pharmacokinetics and organ distribution of intravenous and oral methylene blue
Pharmacokinetics and organ distribution of intravenous and oral methylene blue
复制标题
DOI：
10.1007/s002280000124
复制
发表时间：
2000-06-01
影响因子：
2.9
通讯作者：
Lauterburg, BH
中科院分区：
文献类型：
--
作者：
Peter, C;Hongwan, D;Lauterburg, BH
目的：为了确定静脉注射和口服亚甲蓝的药代动力学和器官分布，这是用来防止异环磷酰胺引起的脑病在oncology.Methods：全血中的亚甲蓝浓度测定使用高效液相色谱法在7名志愿者静脉注射和口服100毫克亚甲蓝与美司钠。结果：静脉注射给药后，亚甲蓝在全血中的时间过程呈多相性，终末半衰期为5.25 h。经口给药后，浓度-时间曲线下面积低得多（9 nmol/min/ml vs 137 nmol/min/ml）。美司钠联合给药（可能通过离子配对影响分布）不会改变药代动力学。静脉注射给药后，亚甲蓝及其无色体的尿排泄量仅中度升高（18% vs 28%剂量）。大鼠十二指肠内注射亚甲蓝后，其肠壁和肝脏中的浓度高于静脉注射亚甲蓝，而全血和脑中的浓度低于静脉注射亚甲蓝。结论：亚甲蓝的器官分布差异是造成口服和静脉注射亚甲蓝后不同药代动力学的主要原因。如果亚甲蓝作用于肝脏（异环磷酰胺主要在肝脏中活化为反应性和潜在毒性代谢物），则口服和静脉注射亚甲蓝可能同样有效。然而，如果作用部位是中枢神经系统，静脉注射亚甲蓝似乎更可取，因为其在脑中的浓度更高。
Objective: To determine the pharmacokinetics and organ distribution of i.v. and oral methylene blue, which is used to prevent ifosfamide-induced encephalopathy in oncology.Methods: The concentration of methylene blue in whole blood was measured using high-performance liquid chromatography in seven volunteers after i.v. and oral administration of 100 mg methylene blue with and without mesna. The distribution of methylene blue in different tissues was measured in rats after intraduodenal and i.v. application.Results: The time course of methylene blue in whole blood after i.v. administration showed a multiphasic time course with an estimated terminal half-life of 5.25 h. Following oral administration, the area under the concentration-time curve was much lower (9 nmol/min/ml vs 137 nmol/min/ml). Co-administration of mesna, which could influence distribution by ion-pairing, did not alter the pharmacokinetics. The urinary excretion of methylene blue and its leucoform was only moderately higher after i.v. administration (18% vs 28% dose). Intraduodenal administration to rats resulted in higher concentrations in intestinal wall and liver but lower concentrations in whole blood and brain than i.v. methylene blue.Conclusions: Differences in organ distribution of methylene blue are mainly responsible for the different pharmacokinetics after oral and i.v, administration. If methylene blue acts in the liver, where ifosfamide is primarily activated to reactive and potentially toxic metabolites, oral and i.v. methylene blue are likely to be equally effective. However, if the site of action is the central nervous system, i.v. methylene blue which results in much higher concentrations in brain seems preferable.