Moulin D E, Inturrisi C E, Foley K M
Ann Neurol. 1986 Aug;20(2):218-22. doi: 10.1002/ana.410200207.
Using an implantable pump system to deliver drugs and sample cerebrospinal fluid (CSF), we assessed rostral redistribution and systemic uptake after intrathecal bolus injection and steady-state infusion of morphine sulfate and the opioid peptide D-Ala2-D-Leu5-enkephalin (DADL) in two patients. Following bolus injection, the mean CSF elimination half-lives for morphine sulfate and DADL were 94 and 115 minutes, respectively. With the catheter tip at L2, the ratio of lumbar to cisternal (L/C) concentrations of morphine sulfate was about 7:1, and with the catheter tip at T10, the L/C ratios of morphine sulfate and DADL were approximately 2:1, indicating that this ratio is dependent in part on the level of intrathecal drug administration. CSF levels of morphine sulfate at steady state were three orders of magnitude higher than those in plasma. The CSF pharmacokinetics of morphine sulfate and DADL are similar, with supraspinal redistribution of these opioids via the CSF likely playing an important role in the generation of analgesia and central nervous system side effects.
我们使用可植入泵系统输送药物并采集脑脊液（CSF）样本，对两名患者鞘内推注和持续输注硫酸吗啡及阿片肽D - Ala2 - D - Leu5 - 脑啡肽（DADL）后的头端再分布和全身摄取情况进行了评估。推注后，硫酸吗啡和DADL的平均脑脊液消除半衰期分别为94分钟和115分钟。导管尖端位于L2时，硫酸吗啡的腰段与脑池段（L/C）浓度比约为7:1，导管尖端位于T10时，硫酸吗啡和DADL的L/C比约为2:1，这表明该比例部分取决于鞘内给药水平。稳态时硫酸吗啡的脑脊液水平比血浆中的高三个数量级。硫酸吗啡和DADL的脑脊液药代动力学相似，这些阿片类药物通过脑脊液向脊髓上的再分布可能在镇痛和中枢神经系统副作用的产生中起重要作用。
