Ashby M, Fleming B, Wood M, Somogyi A
Palliative Care Service, Royal Adelaide Hospital, Australia.
J Pain Symptom Manage. 1997 Sep;14(3):157-67. doi: 10.1016/S0885-3924(97)00020-1.
Plasma morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) concentrations were quantified by high performance liquid chromatography (HPLC) in 36 hospice inpatients receiving morphine orally or subcutaneously. The data were analyzed in relation to dose, serum creatinine, serum gamma glutamyl transferase, and presence or absence of opioid-induced adverse effects. There were significant associations (P < 0.05) between plasma morphine, M3G (subcutaneous route only), and M6G concentrations and dose for both routes of administration. The mean dose-corrected plasma morphine concentration for the subcutaneous group was three times that of the oral group, confirming present oral to subcutaneous dose conversion practices. Nineteen patients experienced symptoms attributed to morphine: nausea and vomiting in ten and acute delirium in nine. Serum creatinine was elevated in patients with adverse effects (P = 0.031), as were the dose-corrected plasma M3G (P = 0.029) and M6G (P = 0.043) concentrations. All seven patients with serum creatinine concentrations above the normal range had symptoms attributed to opioid-induced adverse effects. Plasma M3G, M6G, and dose-corrected plasma M3G and M6G concentrations were significantly (P < 0.001) higher in these patients than in those with normal serum creatinine concentrations. The data indicate that accumulation of M3G and M6G may be a causal or aggravating factor in the nausea and vomiting and cognitive function profile of palliative and terminal care patients with significant renal function impairment.
采用高效液相色谱法（HPLC）对36例口服或皮下注射吗啡的临终关怀住院患者的血浆吗啡、吗啡-3-葡萄糖醛酸苷（M3G）和吗啡-6-葡萄糖醛酸苷（M6G）浓度进行了定量分析。分析了这些数据与剂量、血清肌酐、血清γ-谷氨酰转移酶以及是否存在阿片类药物引起的不良反应之间的关系。血浆吗啡、M3G（仅皮下给药途径）和M6G浓度与两种给药途径的剂量之间均存在显著相关性（P < 0.05）。皮下注射组的平均剂量校正血浆吗啡浓度是口服组的三倍，证实了目前口服至皮下的剂量转换方法。19例患者出现了归因于吗啡的症状：10例出现恶心和呕吐，9例出现急性谵妄。出现不良反应的患者血清肌酐升高（P = 0.031），剂量校正后的血浆M3G（P = 0.029）和M6G（P = 0.043）浓度也升高。血清肌酐浓度高于正常范围的所有7例患者均出现了归因于阿片类药物引起的不良反应的症状。这些患者的血浆M3G、M6G以及剂量校正后的血浆M3G和M6G浓度均显著高于血清肌酐浓度正常的患者（P < 0.001）。数据表明，在有明显肾功能损害且接受姑息和临终护理的患者中，M3G和M6G的蓄积可能是恶心、呕吐以及认知功能障碍的一个因果或加重因素。
