Department of Anesthesiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku and Turku University Hospital, Turku, Finland.
Drugs Aging. 2011 Jan 1;28(1):41-50. doi: 10.2165/11586140-000000000-00000.
Oxycodone is a widely used opioid analgesic, the global use of which has increased several-fold during the last decade. This study was designed to determine the effect of age on the pharmacokinetics of intravenous oxycodone, with special reference to renal function in elderly patients.
We compared the pharmacokinetics of 5 mg of intravenous oxycodone in four groups of 10-11 patients, aged 20-40, 60-70, 70-90 years, undergoing orthopaedic surgery. Plasma concentrations of oxycodone and its noroxycodone, oxymorphone and noroxymorphone metabolites were measured for 24 hours with a liquid chromatography-tandem mass spectrometric method. The cytochrome P450 (CYP) 2D6 genotype of the patients was determined. Glomerular filtration rate (GFR) was estimated on the basis of the age, sex and serum creatinine concentration of the patient.
The pharmacokinetics of oxycodone showed age dependency. In the oldest group, the mean area under the plasma concentration-time curve from time zero to infinity (AUC(∞)) of oxycodone was 80% greater (p < 0.001) and the apparent total body clearance of the drug from plasma (CL) was 34% lower (p < 0.05) than in the youngest group. The mean AUC(∞) of oxycodone was also 30-41% greater in the oldest group than in the age groups of 60-70 and 70-80 years (p < 0.05). Oxycodone plasma concentrations from 8 hours post-dose were >2-fold higher (p < 0.01) in patients aged >80 years than in patients aged 20-40 years. Noroxycodone AUC(∞) was increased in the oldest group compared with patients aged 20-40 and 60-70 years (p < 0.05). There were no significant sex-related differences in any of the pharmacokinetic parameters. Because 37 of the 41 patients were extensive metabolizers through CYP2D6, the effect of the CYP2D6 genotype on oxycodone pharmacokinetics could not be properly assessed. There was a linear correlation between GFR and CL (p < 0.01, coefficient of determination [r(2)] = 0.26), volume of distribution at steady state (p < 0.05, r(2) = 0.19) and AUC(∞) (p < 0.01, r(2) = 0.29) of oxycodone.
Age is an important factor affecting the pharmacokinetics of oxycodone. Following intravenous administration of oxycodone, patients aged >70 years are expected to have, on average, 40-80% higher exposure to oxycodone than young adult patients. Because oxycodone pharmacokinetics are greatly dependent on the age of the patient, it is important to titrate the analgesic dose individually, particularly in the elderly.
羟考酮是一种广泛应用的阿片类镇痛药，在过去十年中，其全球用量增加了数倍。本研究旨在确定年龄对静脉内羟考酮药代动力学的影响，特别关注老年患者的肾功能。
我们比较了 40 名年龄在 20-40 岁、60-70 岁、70-90 岁之间的骨科手术患者，每组 10-11 例，分别静脉给予 5 毫克羟考酮后的药代动力学。采用液相色谱-串联质谱法测定 24 小时内羟考酮及其代谢物去甲羟考酮、羟吗啡酮和去甲羟吗啡酮的血浆浓度。患者的细胞色素 P450（CYP）2D6 基因型也被确定。根据患者的年龄、性别和血清肌酐浓度，估算肾小球滤过率（GFR）。
羟考酮的药代动力学呈现出年龄依赖性。在最年长的一组中，羟考酮的零时刻至无穷大的血浆浓度-时间曲线下面积（AUC（∞））增加了 80%（p < 0.001），药物的表观全身清除率（CL）降低了 34%（p < 0.05）。最年长的一组羟考酮的 AUC（∞）也比年龄在 60-70 岁和 70-80 岁的组高出 30-41%（p < 0.05）。在年龄>80 岁的患者中，羟考酮的血浆浓度从 8 小时后开始>2 倍（p < 0.01）高于年龄在 20-40 岁的患者。与年龄在 20-40 岁和 60-70 岁的患者相比，最年长的一组去甲羟考酮的 AUC（∞）增加（p < 0.05）。在任何药代动力学参数中，都没有发现明显的性别差异。由于 41 名患者中有 37 名是 CYP2D6 的广泛代谢者，因此无法正确评估 CYP2D6 基因型对羟考酮药代动力学的影响。GFR 与 CL（p < 0.01，决定系数 [r（2）] = 0.26）、稳态分布容积（p < 0.05，r（2）= 0.19）和 AUC（∞）（p < 0.01，r（2）= 0.29）之间存在线性相关。
年龄是影响羟考酮药代动力学的一个重要因素。静脉给予羟考酮后，年龄>70 岁的患者预计比年轻成年患者的羟考酮暴露量增加 40-80%。由于羟考酮的药代动力学受患者年龄的影响很大，因此在老年患者中，重要的是要个体化滴定镇痛剂量。
