Wolff T, Samuelsson H, Hedner T
Department of Anaesthesia, Sahlgrenska University Hospital, Göteborg, Sweden.
Pain. 1996 Dec;68(2-3):209-16. doi: 10.1016/s0304-3959(96)03102-8.
Plasma and cerebrospinal fluid (CSF) steady-state concentrations (Css) of morphine (M) and the main metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), were determined by high performance liquid chromatography (HPLC) in 21 cancer patients treated with chronic subcutaneous morphine infusion. There was a moderate, but statistically significant correlation between the daily dose of morphine and the concentrations of morphine, M3G and M6G in CSF. A poorer correlation to concentrations were seen in plasma. The mean +/- SEM CSF/plasma morphine concentration ratio was 0.36 +/- 0.07. In plasma and CSF, the mean steady state concentration of M3G but not M6G substantially exceeded that of morphine where the mean CSF M/M3G/M6G ratio was 1:15:0.5 (molar basis), and the mean plasma ratio was M/M3G/M6G 1:31:3 (molar basis). The mean M3G and M6G concentrations in CSF were approximately 8 and 10% of those found in plasma, but there was a wide interindividual variation. Plasma concentrations of both morphine glucuronides were positively correlated to serum creatinine. Neither pain intensity, evaluated by visual analogue scale (VAS), nor side effects showed any relationship to the CSF M3G concentrations, M3G/M or the M3G/M6G ratios. We conclude that during steady state subcutaneous administration of morphine, there is a large interindividual variation in plasma morphine with poor relationship to the daily administered dose. In CSF this correlation was more evident. Plasma and CSF concentrations of M3G and CSF concentrations of M6G correlated with administered morphine dose. There was an accumulation of both morphine glucuronides in patients with elevated serum creatinine. Measurements of morphine, M3G and M6G in CSF did not show any overt relationship to analgesia or side effects.
采用高效液相色谱法（HPLC）测定了21例接受慢性皮下吗啡输注治疗的癌症患者血浆和脑脊液（CSF）中吗啡（M）及其主要代谢产物吗啡-3-葡萄糖醛酸苷（M3G）和吗啡-6-葡萄糖醛酸苷（M6G）的稳态浓度（Css）。吗啡的日剂量与脑脊液中吗啡、M3G和M6G的浓度之间存在中等程度但具有统计学意义的相关性。在血浆中观察到与浓度的相关性较差。脑脊液/血浆吗啡浓度的平均±标准误比值为0.36±0.07。在血浆和脑脊液中，M3G的平均稳态浓度显著超过吗啡，而M6G则不然，脑脊液中M/M3G/M6G的平均比值为1:15:0.5（摩尔比），血浆中的平均比值为M/M3G/M6G 1:31:3（摩尔比）。脑脊液中M3G和M6G的平均浓度约为血浆中浓度的8%和10%，但个体间差异很大。两种吗啡葡萄糖醛酸苷的血浆浓度与血清肌酐呈正相关。通过视觉模拟评分法（VAS）评估的疼痛强度和副作用均与脑脊液M3G浓度、M3G/M或M3G/M6G比值无关。我们得出结论，在吗啡皮下稳态给药期间，血浆吗啡存在较大的个体间差异，与每日给药剂量的关系较差。在脑脊液中这种相关性更明显。M3G的血浆和脑脊液浓度以及M6G的脑脊液浓度与给药的吗啡剂量相关。血清肌酐升高的患者中两种吗啡葡萄糖醛酸苷均有蓄积。脑脊液中吗啡、M3G和M6G的测量结果与镇痛或副作用无明显关系。
