Komatsu Toshiaki, Kokubun Hideya, Suzuki Ai, Takayanagi Risa, Yamada Yasuhiko, Matoba Motohiro, Yago Kazuo
Department of Pharmacy, Kitasato University Hospital, Kanagawa, Japan.
J Pain Palliat Care Pharmacother. 2012 Sep;26(3):220-5. doi: 10.3109/15360288.2012.702200.
Oxycodone is an opioid widely prescribed to cancer patients for pain relief. However, the pharmacokinetics of oxycodone has not been sufficiently examined. Therefore the aim of this work was to study population pharmacokinetics of oxycodone in patients with cancer pain. The authors analyzed 108 serum oxycodone samples of 33 individuals with nonlinear mixed-effects model (NONMEM). Population pharmacokinetics was calculated using the one-compartment model of clearance, volume of distribution, bioavailability, absorption constant rate, and lag time. An exponential error model was used to determine interindividual variability and a relative error model was applied to assess residual variability. Population pharmacokinetics of oxycodone at the end point were as follows: CL(L/h) = 10.7 × [1 + (2 - Child-Pugh Classification)] (Class: A = 0, B = 1, C = 2); V(d) (L) = 193; k(a) (h(-1)) = 0.336; T(lag) (h) = 0.859; F (%) = 63.9. Interindividual variability was CL: 30.5%, V(d): 44.6%, and F: 37.0%, and residual variability was 16.2%. As the total clearance in patients with liver dysfunction (Child-Pugh class B) was reduced to 33.3%, serum concentration of oxycodone increased by 1.5. Therefore, it became clear that dose adjustments are essential when treating patients with liver dysfunction. These findings suggest that population parameters are useful for evaluating pharmacokinetics of oxycodone in patients with cancer pain.
羟考酮是一种广泛用于癌症患者缓解疼痛的阿片类药物。然而，羟考酮的药代动力学尚未得到充分研究。因此，这项工作的目的是研究癌症疼痛患者中羟考酮的群体药代动力学。作者使用非线性混合效应模型（NONMEM）分析了33名个体的108份血清羟考酮样本。使用清除率、分布容积、生物利用度、吸收恒定速率和滞后时间的单室模型计算群体药代动力学。使用指数误差模型确定个体间变异性，并应用相对误差模型评估残余变异性。终点时羟考酮的群体药代动力学如下：CL（L/h）=10.7×[1 +（2 - Child-Pugh分级）]（分级：A = 0，B = 1，C = 2）；V（d）（L）= 193；k（a）（h⁻¹）= 0.336；T（lag）（h）= 0.859；F（%）= 63.9。个体间变异性为CL：30.5%，V（d）：44.6%，F：37.0%，残余变异性为16.2%。由于肝功能不全患者（Child-Pugh B级）的总清除率降低至33.3%，羟考酮的血清浓度增加了1.5倍。因此，很明显，在治疗肝功能不全患者时进行剂量调整至关重要。这些发现表明，群体参数有助于评估癌症疼痛患者中羟考酮的药代动力学。
