Ther Clin Risk Manag. 2007 Oct;3(5):961-7.
An increased and prolonged duration of pain relief after morphine administration has been found in elderly patients. Whether this is due to alterations in pharmacokinetics, receptor binding profile or other factors remains unsolved. The aims were to elucidate the pharmacokinetics after intravenous administration of morphine and oxycodone in elderly patients older than 70 years.
A randomized non-blinded study with 16 patients aged older than 70 years scheduled for elective hip replacement receiving morphine or oxycodone 0.05 mg/kg as an IV infusion over 15 minutes.
A 2-compartment pharmacokinetic model best described the disposition of morphine and oxycodone. The estimated elimination half-lives for morphine and oxycodone were (mean +/- SD) 2.7 +/- 3.6 (range 0.8-11.6) and 3.1 +/- 1.3 (range 1.1-4.8) hr, respectively. Volume of distribution at steady state was estimated to be 243 +/- 256 and 277 +/- 187 L, and clearance to be 1748 +/- 623 and 1206 +/- 546 ml/min for morphine and oxycodone, respectively.
The increased and prolonged duration of pain relief after morphine administration seen in some elderly patients cannot, based on these findings, be ascribed to changes in the pharmacokinetic parameters between elderly and younger patients. Similar for oxycodone, no changes in the pharmacokinetic could be found when comparing the parameters found in elderly patients with those from younger healthy volunteers. A great variability within the individual pharmacokinetic parameters was seen for both drugs. Therefore, we recommend that treatment with morphine and oxycodone in elderly patients is initiated very conservatively and is titrated slowly to effect.
在老年患者中,吗啡给药后的疼痛缓解时间延长。这是否是由于药代动力学、受体结合谱或其他因素的改变所致,目前仍未解决。目的是阐明 70 岁以上老年患者静脉注射吗啡和羟考酮后的药代动力学。
一项随机、非盲研究,纳入 16 名年龄大于 70 岁的择期髋关节置换术患者,接受吗啡或羟考酮 0.05mg/kg 静脉输注 15 分钟。
吗啡和羟考酮的药代动力学呈二室模型。吗啡和羟考酮的估计消除半衰期分别为(均值±SD)2.7±3.6(范围 0.8-11.6)和 3.1±1.3(范围 1.1-4.8)小时。稳态时的分布容积分别为 243±256 和 277±187 L,清除率分别为 1748±623 和 1206±546 ml/min。
基于这些发现,一些老年患者中吗啡给药后疼痛缓解时间延长并不能归因于老年患者与年轻患者之间药代动力学参数的变化。对于羟考酮,与年轻健康志愿者相比,在比较老年患者的药代动力学参数时,未发现药代动力学的变化。两种药物的个体药代动力学参数均存在较大的变异性。因此,我们建议老年患者使用吗啡和羟考酮时应非常保守地开始治疗,并缓慢滴定至有效剂量。