Klepstad P, Dale O, Kaasa S, Zahlsen K, Aamo T, Fayers P, Borchgrevink P C
Department of Anesthesia and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
Acta Anaesthesiol Scand. 2003 Jul;47(6):725-31. doi: 10.1034/j.1399-6576.2003.00138.x.
In order to make treatment decisions physicians should have knowledge about the relations between patient characteristics and drug disposition. Dose, route of administration, gender, age and renal function are reported to influence the serum concentrations of morphine, morphine-6-glucurnide (M6G) and morphine-3-glucuronide (M3G) during chronic treatment of cancer pain. These factors, however, are not evaluated in studies with a sample size sufficient to explore predictive factors.
Three hundred consecutive morphine users admitted because of a malignant disease were recruited. The relations of serum concentrations of morphine, M6G and M3G to patient characteristics (gender, age, weight, renal function, liver function, dose, route of administration) were explored, and regression analysis performed to investigate whether these characteristics predicted serum concentrations obtained during routine clinical drug monitoring.
Morphine dose was associated with serum concentrations of morphine (r = 0.69), M6G (r = 0.76) and M3G (r = 0.76). Oral morphine resulted in higher dose-adjusted M6G and M3G serum concentrations compared with s.c. morphine. Creatinine serum concentrations correlated with serum concentrations of M6G and M3G. Dose and route of administration predicted morphine serum concentrations, while dose and renal function predicted M6G and M3G serum concentrations. Age was an additional factor predicting M3G concentrations. Dose was the only factor that explained a clinically significant part of the observed variability.
Patient characteristics predict only minor parts of the variability of morphine, M3G and M6G serum concentrations observed during routine clinical drug-monitoring in cancer patients.
为了做出治疗决策，医生应了解患者特征与药物处置之间的关系。据报道，在癌症疼痛的长期治疗过程中，剂量、给药途径、性别、年龄和肾功能会影响吗啡、吗啡 - 6 - 葡萄糖醛酸苷（M6G）和吗啡 - 3 - 葡萄糖醛酸苷（M3G）的血清浓度。然而，在样本量足以探索预测因素的研究中，并未对这些因素进行评估。
招募了300名因恶性疾病入院的连续使用吗啡的患者。探讨了吗啡、M6G和M3G的血清浓度与患者特征（性别、年龄、体重、肾功能、肝功能、剂量、给药途径）之间的关系，并进行回归分析，以研究这些特征是否能预测常规临床药物监测期间获得的血清浓度。
吗啡剂量与吗啡（r = 0.69）、M6G（r = 0.76）和M3G（r = 0.76）的血清浓度相关。与皮下注射吗啡相比，口服吗啡导致剂量调整后的M6G和M3G血清浓度更高。血清肌酐浓度与M6G和M3G的血清浓度相关。剂量和给药途径可预测吗啡血清浓度，而剂量和肾功能可预测M6G和M3G血清浓度。年龄是预测M3G浓度的另一个因素。剂量是解释观察到的变异性中具有临床意义部分的唯一因素。
在癌症患者的常规临床药物监测期间，患者特征仅能预测观察到的吗啡、M3G和M6G血清浓度变异性的一小部分。
