Ramu A, Fusner J E
Isr J Med Sci. 1979 Jun;15(6):494-9.
A pharmacokinetic model has been established in which plasma methotrexate (MTX) concentrations following intrathecal administration are predicted. The model is based upon cerebrospinal fluid MTX concentrations following intrathecal injection of MTX, and plasma MTX levels subsequent to i.v. injection of the drug in dogs. Anticipated plasma MTX levels were compared with actual measured concentrations. The model predicts changes in the plasma MTX concentration curve as a result of varying of the injected dose, reduction in plasma MTX clearance, and reduced transfer of MTX from cerebrospinal fluid to the blood. It is suggested that plasma MTX levels be measured at 3, 5, 7 and 10 h following intrathecal injection to facilitate an early assessment of unusually slow plasma MTX decay. Thus, administration of leucovorin, to prevent systemic toxicity, may be more rapidly commenced. Also, if such measurements indicate that the transfer of MTX from cerebrospinal fluid to the blood is reduced. MTX dose of the subsequent intrathecal injections should be reduced to minimize risks of systemic toxicity and neurotoxicity.
已建立了一个药代动力学模型，用于预测鞘内注射甲氨蝶呤（MTX）后的血浆MTX浓度。该模型基于鞘内注射MTX后的脑脊液MTX浓度以及静脉注射该药物后犬的血浆MTX水平。将预期的血浆MTX水平与实际测量浓度进行比较。该模型预测了由于注射剂量变化、血浆MTX清除率降低以及MTX从脑脊液向血液的转运减少导致的血浆MTX浓度曲线变化。建议在鞘内注射后3、5、7和10小时测量血浆MTX水平，以便早期评估血浆MTX异常缓慢的衰减情况。因此，可以更快地开始给予亚叶酸钙以预防全身毒性。此外，如果此类测量表明MTX从脑脊液向血液的转运减少，则应降低后续鞘内注射的MTX剂量，以将全身毒性和神经毒性风险降至最低。
