Klepstad P, Kaasa S, Borchgrevink P C
Department of Anaesthesiology, University Hospital of Trondheim, Norwegian University of Science and Technology, Trondheim N-7006, Norway.
Eur J Clin Pharmacol. 2000 Jan;55(10):713-9. doi: 10.1007/s002280050003.
To investigate the serum concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) and the relationships between serum concentrations and clinical effects associated with start of morphine treatment in cancer patients.
Forty patients with malignant disease and intolerable pain on weak opioids (codeine/dextropropoxyphen) were included. After a wash-out period, titration with immediate-release (IR) morphine was started. When a stable dose was achieved, the morphine treatment was changed to slow-release (SR) morphine in equivalent daily dosages. Clinical data and serum concentrations of morphine, M3G and M6G were obtained at the end of the IR and SR morphine treatment periods.
The mean trough serum morphine concentration associated with pain relief was 66 nmol/l. The corresponding mean concentrations of M6G and M3G were 257 nmol/l and 1943 nmol/l, respectively. Morphine serum trough concentrations showed a 33-fold variation. Seventy percent of the variation was predicted in a model including age, daily morphine dose and M6G/morphine ratio as independent variables. No associations were observed between side effects and serum concentrations of morphine and its metabolites.
In this study, a mean serum trough morphine concentration of 66 nmol/l was associated with satisfactory pain relief when disease progression required an increase in intensity of pain therapy from step II to step III in the World Health Organization pain ladder. An increased ratio of M6G to morphine serum concentrations predicted lower effective serum morphine concentrations at the time of satisfactory pain relief. This observation supports that M6G contributes to the pain control produced by oral morphine in patients with pain caused by malignant disease.
研究癌症患者吗啡治疗开始时血清中吗啡、吗啡 - 3 - 葡萄糖醛酸苷（M3G）和吗啡 - 6 - 葡萄糖醛酸苷（M6G）的浓度，以及血清浓度与临床疗效之间的关系。
纳入40例患有恶性疾病且对弱阿片类药物（可待因/右丙氧芬）止痛效果不佳的患者。经过洗脱期后，开始用即释型（IR）吗啡进行滴定。当达到稳定剂量时，将吗啡治疗改为等效日剂量的缓释型（SR）吗啡。在IR和SR吗啡治疗期结束时获取临床数据以及吗啡、M3G和M6G的血清浓度。
与疼痛缓解相关的平均血清吗啡谷浓度为66 nmol/l。M6G和M3G的相应平均浓度分别为257 nmol/l和1943 nmol/l。吗啡血清谷浓度显示出33倍的差异。在一个以年龄、每日吗啡剂量和M6G/吗啡比值作为自变量的模型中，70%的差异可被预测。未观察到副作用与吗啡及其代谢产物血清浓度之间存在关联。
在本研究中，当疾病进展需要将世界卫生组织疼痛阶梯中疼痛治疗强度从II级提高到III级时，平均血清吗啡谷浓度为66 nmol/l与满意的疼痛缓解相关。M6G与吗啡血清浓度比值增加预示着在疼痛得到满意缓解时有效血清吗啡浓度较低。这一观察结果支持M6G有助于口服吗啡对恶性疾病所致疼痛患者的疼痛控制。
