Faura C C, Moore R A, Horga J F, Hand C W, McQuay H J
Oxford Pain Relief Unit, Nuffield Department of Anaesthesia, University of Oxford, Churchill Hospital, United Kingdom.
J Pain Symptom Manage. 1996 Feb;11(2):95-102. doi: 10.1016/0885-3924(95)00148-4.
The relationships between plasma morphine and metabolite (M3G and M6G) concentrations and analgesic efficacy were investigated in an open study of 39 cancer pain patients receiving chronic oral morphine therapy with either morphine sulfate solution or controlled-release morphine tablets. There were no differences in morphine, metabolite kinetics, or analgesic efficacy between equivalent doses of conventional or controlled-release formulations. The increase in morphine plasma concentration after a dose (1 hr for normal release, 2 hr for controlled release) was correlated significantly with the dose of morphine (r = 0.914, P < 0.001). There was a significant reduction in pain intensity (P < 0.05) and increase in pain relief (P < 0.001) after the dose of morphine administration, when compared with the predose score. One-half of the patients had mild and tolerable adverse effects. Patients were classified by mean pain relief between doses as having optimal, moderate, or poor pain control. No simple relationship was found between morphine plasma concentration and pain control. Morphine plus M6G concentrations in the "optimal control" group (751.2 +/- 194 nmol/L), however, were more than twice those found in the "moderate control" group (276.9 +/- 41.9 nmol/L) (P < 0.05), and no patient in the moderate control group had a morphine plus M6G concentration greater than 405 nmol/L. These results support the importance of M6G in morphine analgesia. For these hospitalized patients, there appeared to be a therapeutic range of morphine plus M6G plasma concentrations for optimal pain control with a lower limit of 400 nmol/L predose.
在一项开放性研究中，对39例接受硫酸吗啡溶液或控释吗啡片慢性口服吗啡治疗的癌症疼痛患者，研究了血浆吗啡及其代谢物（M3G和M6G）浓度与镇痛效果之间的关系。等效剂量的传统剂型或控释剂型在吗啡、代谢物动力学或镇痛效果方面无差异。给药后吗啡血浆浓度的升高（普通释放为1小时，控释为2小时）与吗啡剂量显著相关（r = 0.914，P < 0.001）。与给药前评分相比，给予吗啡剂量后疼痛强度显著降低（P < 0.05），疼痛缓解程度显著增加（P < 0.001）。一半的患者有轻度且可耐受的不良反应。根据两次给药间的平均疼痛缓解情况，将患者分为疼痛控制最佳、中等或较差。未发现吗啡血浆浓度与疼痛控制之间有简单的关系。然而，“最佳控制”组的吗啡加M6G浓度（751.2±194 nmol/L）是“中等控制”组（276.9±41.9 nmol/L）的两倍多（P < 0.05），且中等控制组中没有患者的吗啡加M6G浓度大于405 nmol/L。这些结果支持了M6G在吗啡镇痛中的重要性。对于这些住院患者，似乎存在一个吗啡加M6G血浆浓度的治疗范围，以实现最佳疼痛控制，给药前下限为400 nmol/L。
