Scheufler E, Zetler G, Iven H
Pharmacology. 1981;23(2):75-81. doi: 10.1159/000137531.
After intravenous injection of 31 mg/kg methotrexate (MTX), its concentrations were determined in plasma, liver, kidney, bone marrow, stomach, duodenum, jejunum, colon and muscle up to 23 days, using an enzymatic assay. Plasma pharmacokinetics were described by a triexponential function, with a terminal half-life of 4.2 h. Up to 1.5 h after injection, the initial rapid decline of MTX concentrations in bone marrow, kidney, and liver roughly paralleled that in plasma. The terminal half-life of MTX in bone marrow was greatly prolonged (37 h), while MTX remained nearly constant in liver (0.57 microgram/ml) and kidney (0.53 microgram/ml) from 6 h to 23 days. In the intestines, luminal as well as tissue MTX concentrations were determined. The stomach showed a triexponential decay of tissue MTX and low luminal concentrations throughout. In the duodenum, the middle of jejunum, and the colon tissue MTX seemed to follow a bi- or triexponential function. However, high luminal concentrations due to MTX biliary excretion, when reaching a given intestinal portion, increased the MTX tissue concentration in this segment.
静脉注射31mg/kg甲氨蝶呤（MTX）后，采用酶法测定了长达23天的血浆、肝脏、肾脏、骨髓、胃、十二指肠、空肠、结肠和肌肉中的MTX浓度。血浆药代动力学用三指数函数描述，终末半衰期为4.2小时。注射后1.5小时内，骨髓、肾脏和肝脏中MTX浓度的初始快速下降与血浆中的大致平行。MTX在骨髓中的终末半衰期大大延长（37小时），而从6小时到23天，MTX在肝脏（0.57微克/毫升）和肾脏（0.53微克/毫升）中几乎保持恒定。在肠道中，测定了肠腔和组织中的MTX浓度。胃组织中的MTX呈现三指数衰减，且整个过程中肠腔浓度较低。在十二指肠、空肠中部和结肠，组织MTX似乎遵循双指数或三指数函数。然而，由于MTX经胆汁排泄产生的高肠腔浓度，当到达特定肠段时，会增加该段的MTX组织浓度。
