Wolff Tomas, Samuelsson Håkan, Hedner Thomas
Pain Sections, Department of Anaesthesia, Central Hospitals, Skövde and Borås, Sweden Department of Clinical Pharmacology, Sahlgrenska University Hospital, Göteborg, Sweden.
Pain. 1995 Aug;62(2):147-154. doi: 10.1016/0304-3959(94)00268-J.
In 34 cancer patients treated with chronic slow-release oral morphine, plasma and cerebrospinal fluid (CSF) minimum steady-state concentrations of morphine (M), morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were determined by high-performance liquid chromatography (HPLC). Both plasma and CSF morphine, M3G and M6G, concentrations were linearly related to dose of morphine. At steady state, the mean +/- SEM CSF/plasma morphine concentration ratio was 0.8 +/- 0.1. In plasma and CSF, the mean steady-state concentrations of M3G and M6G substantially exceeded those of morphine where the mean CSF M/M3G/M6G ratio was 1:47:5 (weight basis), 1:34:4 (molar basis) and the mean plasma ratio was M/M3G/M6G 1:150:23 (weight basis), 1:109:17 (molar basis). The mean M3G and M6G concentrations in CSF at steady state were 15-18% of those found in plasma. Pain relief, evaluated by a visual analogue scale (VAS), did not correlate with the CSF M3G concentrations or with the M3G/M ratio. Since CSF M6G concentrations were high, M6G could, however, contribute to pain relief. We conclude that after oral administration of slow-release morphine, there is a significant passage of the morphine glucuronide metabolites to the CSF and that the M3G and M6G metabolites in CSF are in the concentration range where they may have an influence on analgesia.
在34例接受慢性缓释口服吗啡治疗的癌症患者中，采用高效液相色谱法（HPLC）测定了血浆和脑脊液（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。血浆和脑脊液中的吗啡、M3G和M6G浓度均与吗啡剂量呈线性相关。稳态时，平均±标准误脑脊液/血浆吗啡浓度比为0.8±0.1。在血浆和脑脊液中，M3G和M6G的平均稳态浓度大大超过吗啡的浓度，其中脑脊液中M/M3G/M6G平均比值为1:47:5（重量比）、1:34:4（摩尔比），血浆平均比值为M/M3G/M6G 1:150:23（重量比）、1:109:17（摩尔比）。脑脊液中稳态时M3G和M6G的平均浓度为血浆中浓度的15 - 18%。通过视觉模拟评分法（VAS）评估的疼痛缓解与脑脊液中M3G浓度或M3G/M比值无关。然而，由于脑脊液中M6G浓度较高，M6G可能有助于缓解疼痛。我们得出结论，口服缓释吗啡后，吗啡葡萄糖醛酸代谢产物可大量进入脑脊液，且脑脊液中的M3G和M6G代谢产物浓度范围可能对镇痛有影响。
