A Pharmacokinetic and Pharmacodynamic Study of Oral Oxycodone in a Human Experimental Pain Model of Hyperalgesia
A Pharmacokinetic and Pharmacodynamic Study of Oral Oxycodone in a Human Experimental Pain Model of Hyperalgesia
复制标题
DOI：
10.2165/11536610-000000000-00000
复制
发表时间：
2010-01-01
影响因子：
4.5
通讯作者：
Drewes, Asbjorn M.
中科院分区：
文献类型：
--
作者：
Olesen, Anne E.;Upton, Richard;Drewes, Asbjorn M.
背景与目的羟考酮的药代动力学/药效学特性不如其他阿片类药物，而且羟考酮的药效学特征会受到疼痛系统变化的影响，例如痛觉过敏。方法24名健康受试者口服羟考酮（15mg）或安慰剂，采用多模态、多组织模式评估药效学，从皮肤（热）、肌肉（压力）和内脏（热和电）三个方面评估疼痛。在给药前和给药后5、10、15、30、45、60、90和120分钟，取食管静脉血样本，定量测定羟考酮血药浓度。结果羟考酮血药浓度可以用单室模型描述，但考虑到研究的必然短时间尺度，浓度是由线性插值对后续药效学模型时间痛苦的改变措施安慰剂的研究是由线性或二次函数的时间进程疼痛措施羟考酮的手臂被安慰剂的时间进程+浓度效应关系,要么是零(没有药物作用),线性或最大效应(E-max)梅尔三四个痛苦的措施,结论与安慰剂相比，羟考酮在所有疼痛测量指标上都有可测量的效果，且呈线性浓度-效应关系，无效应延迟，这可能表明羟考酮具有初始外周镇痛作用
Background and Objective Oxycodone is not as well characterized, with respect to its pharmacokinetic/pharmacodynamic properties, as other opioids Moreover, the pharmacodynamic profile of oxycodone can be affected by changes in the pain system, e g hyperalgesia Therefore, the aim of this study was to investigate the pharmacokinetic/pharmacodynamic profiles of oxycodone in a human experimental pain model of hyperalgesiaMethods Twenty-four healthy subjects received oral oxycodone (15 mg) or placebo Pharmacodynamics were assessed utilizing a multimodal, multi-tissue paradigm where pain was assessed from skin (heat), muscle (pressure) and viscera (heat and electricity) before and 30, 60 and 90 minutes after induction of generalized hyperalgesia evoked by perfusion of acid and capsaicin in the oesophagus Venous blood samples were obtained for quantification of oxycodone plasma concentrations before and 5, 10, 15, 30, 45, 60, 90 and 120 minutes after drug administrationResults Oxycodone blood concentrations could be described by a one-compartment model but, given the necessarily short timescale of the study, the concentrations were represented by linear interpolation for subsequent pharmacodynamic models Time-dependent changes in the pain measures in the placebo arm of the study were represented by linear or quadratic functions The time course of the pain measures in the oxycodone arm was taken to be the time course for the placebo arm plus a concentration-effect relationship that was either zero (no drug effect), linear or a maximum effect (E-max) modelFor three of the four pain measures, there was a time-dependent change after administration of placebo (e g due to the development of generalized hyperalgesia)Conclusion There was a measurable effect of oxycodone, compared with placebo, on all pain measures, and a linear concentration-effect relationship without an effect delay was demonstrated This could indicate an initial peripheral analgesic effect of oxycodone