Serum and cerebrospinal fluid morphine pharmacokinetics after single doses of intravenous and intramuscular morphine after hip replacement surgery
Serum and cerebrospinal fluid morphine pharmacokinetics after single doses of intravenous and intramuscular morphine after hip replacement surgery
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DOI：
10.1007/s00228-007-0329-x
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发表时间：
2007-09-01
影响因子：
2.9
通讯作者：
Klepstad, P.
中科院分区：
文献类型：
--
作者：
Dale, O.;Thoner, J.;Klepstad, P.
目的比较术后静脉注射和肌肉注射吗啡后血清及脑脊液中吗啡代谢物浓度的时间变化。方法：这是一项随机、双盲、双假人研究，研究对象为髋关节置换术患者。吗啡（M, 10 mg）静脉注射（IV）或肌肉注射（IM）。在给药后10、30、60和120分钟同时抽取动脉血和脑脊液样本（来自脊髓导管）。吗啡及其代谢物[吗啡-3-葡糖苷（M-3-G）、吗啡-6-葡糖苷（M-6-G）和去甲吗啡（NM）]采用有效的液相色谱-串联质谱法测定。结果共纳入38例患者，其中男性13例，女性25例，静脉注射组20例，静脉注射组18例。注射后10 min血清M浓度持续高于静脉注射，注射后45 min血清M-3- g和M-6- g浓度超过静脉注射。未找到NM。脑脊液中未发现代谢物。静脉注射后脑脊液吗啡浓度和脑脊液/血清浓度比均高于静脉注射。静脉注射和IM后，平均AUC(CSF)/AUC（血清）（0 ~ 120 min）浓度比分别为0.18和0.09。结论静脉给药后10min吗啡对脑脊液的吸收量明显高于静脉给药后10min吗啡对脑脊液的吸收量。较高的脑脊液浓度可能是由静脉注射吗啡后初始较高的吗啡血/脑脊液梯度引起的。药代动力学结果与静脉注射吗啡比静脉注射吗啡具有更迅速和更广泛的初始效应相一致。
Aim To compare the time course of morphine and metabolite concentrations in serum and cerebrospinal fluid (CSF) after intravenous and intramuscular administration after surgery.Methods This was a randomized double-blind, double-dummy study in patients who had undergone hip replacement surgery. Morphine (M, 10 mg) was administered intravenously (IV) or intramuscularly (IM). Arterial blood and CSF samples (from a spinal catheter) were drawn simultaneously at 10, 30, 60, and 120 min after administration. Morphine and metabolites [morphine-3-glucuronide (M-3-G), morphine-6-glucuronide (M-6-G), and normorphine (NM)] were determined by a validated liquid chromatography-tandem mass spectrometry method.Results Thirty-eight patients were included: 13 men and 25 women, 20 in the IV, 18 in the IM group. Serum concentrations of M after 10 min were consistently higher after IM than IV, concentrations of M-3-G and M-6-G after IM surpassed those of IV after 45 min. NM was not found. None of the metabolites was found in CSF. CSF morphine concentrations and CSF/serum concentration ratios were consistently higher after IV compared to IM. The mean AUC(CSF)/AUC(serum) (0-120 min) concentration ratios were 0.18 and 0.09 after IV and IM, respectively.Conclusion The uptake of morphine to the CSF was consistently higher after IV administration than after IM already after 10 min. The higher CSF concentration may be caused by an initially higher morphine blood/CSF gradient following IV morphine injection. The pharmacokinetic findings are compatible with a more rapid and extensive initial effect of IV morphine compared with IM.