Samuelsson Håkan, Hedner Thomas, Venn Richard, Michalkiewicz Andrew
Department of Anaesthesia, Central Hospital, BoråsSweden Department of Clinical Pharmachology, Sahlgrenska University Hospital, GöteborgSweden Department of Pain Research Institute, LiverpoolUK.
Pain. 1993 Feb;52(2):179-185. doi: 10.1016/0304-3959(93)90129-D.
Thirty-five cancer patients, treated with chronic epidural morphine, were assayed for plasma and cerebrospinal fluid (CSF) minimum steady-state concentrations (Css min) of morphine (M), morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) by high performance liquid chromatography (HPLC). A linear dose-concentration relationship was found for the 3 substances in plasma and for morphine and M3G in CSF. The mean +/- S.E.M. CSF/plasma morphine ratio was 158 +/- 43. In CSF, the concentrations of morphine exceeded those of the metabolites substantially and, normalized to morphine, the mean CSF M/M3G/M6G ratio was 1:0.05:0.02. In plasma, the metabolite concentrations were higher than the parent drug and the plasma M/M3G/M6G ratio was 1:12:3. The mean M3G and M6G concentrations in CSF were 40-60% of those found in plasma. Indication of cerebral formation of M3G was found in 1 patient. Pain relief, evaluated by a visual analogue scale (VAS), did not correlate with the CSF M3G concentrations or with the M3G/M ratio. CSF M6G concentrations were low and did not contribute to any detectable analgesia. We conclude that after epidural administration of morphine, the M3G and M6G metabolites in CSF are low compared to unchanged morphine and seem to have little influence on analgesia. However, the fact that a significant passage of the glucuronide metabolites occurs to the CSF may indicate a role in morphine analgesia after other routes of administration.
对35例接受慢性硬膜外吗啡治疗的癌症患者，采用高效液相色谱法（HPLC）测定血浆和脑脊液（CSF）中吗啡（M）、吗啡-3-葡萄糖醛酸苷（M3G）和吗啡-6-葡萄糖醛酸苷（M6G）的最低稳态浓度（Css min）。在血浆中发现这3种物质以及脑脊液中的吗啡和M3G存在线性剂量-浓度关系。脑脊液/血浆吗啡的平均±标准误比值为158±43。在脑脊液中，吗啡浓度大大超过代谢物浓度，以吗啡标准化后，脑脊液中M/M3G/M6G的平均比值为1:0.05:0.02。在血浆中，代谢物浓度高于母体药物，血浆中M/M3G/M6G的比值为1:12:3。脑脊液中M3G和M6G的平均浓度为血浆中所测浓度的40%-60%。在1例患者中发现有M3G脑内形成的迹象。通过视觉模拟评分法（VAS）评估的疼痛缓解情况与脑脊液中M3G浓度或M3G/M比值无关。脑脊液中M6G浓度较低，对任何可检测到的镇痛作用均无贡献。我们得出结论，硬膜外给予吗啡后，脑脊液中的M3G和M6G代谢物与未改变的吗啡相比含量较低，似乎对镇痛作用影响不大。然而，葡萄糖醛酸苷代谢物大量进入脑脊液这一事实可能表明其在其他给药途径后的吗啡镇痛中发挥作用。
