University of California, San Diego (UCSD), Skaggs School of Pharmacy & Pharmaceutical Sciences, San Diego, CA, USA.
J Anal Toxicol. 2012 May;36(4):232-8. doi: 10.1093/jat/bks022.
The object of this study was to evaluate the metabolism of oxycodone to oxymorphone in a pain patient population using a quantitative liquid chromatography-tandem mass spectrometry analysis of 32,656 urine specimens obtained from pain patients between March 2008 and Feb 2010. The observed excretion was modeled using logarithmic transformation and approximated a Gaussian distribution. Oxycodone excretion into urine had a geometric mean of 1.93 mg/g of creatinine and oxymorphone had a value of 0.41 mg/g of creatinine. Increasing concentrations of oxycodone correlated with a smaller proportion of oxymorphone excretion suggesting saturation of oxycodone metabolism. Urine samples containing oxycodone without oxymorphone allowed an estimation of the proportion of poor metabolizers (2.4 ± 2.1%) in the population. A similar analysis of samples containing oxymorphone without oxycodone gave an estimate of the proportion of ultra-rapid metabolizers (1.8 ± 1.1%) in the population. Samples with concentrations of oxycodone above 10 mg/g of creatinine showed a sub-population of subjects with metabolic ratios roughly 100-fold less than the linear predictive model in this study. This study describes typical ranges for oxycodone and oxymorphone in urine, and showed that it is possible to identify fast or slow metabolizers who may be at risk for adverse events.
本研究旨在通过对 2008 年 3 月至 2010 年 2 月期间从疼痛患者中获得的 32656 份尿液标本进行定量液相色谱-串联质谱分析，评估疼痛患者人群中羟考酮转化为羟吗啡酮的代谢情况。观察到的排泄量通过对数转换进行建模，并近似符合高斯分布。尿液中羟考酮的排泄量几何平均值为 1.93mg/g 肌酐，羟吗啡酮的排泄量值为 0.41mg/g 肌酐。羟考酮浓度的增加与羟吗啡酮排泄比例的减小相关，表明羟考酮代谢达到饱和。尿液样本中仅含有羟考酮而不含羟吗啡酮，可估算人群中代谢不良者的比例（2.4±2.1%）。对仅含有羟吗啡酮而不含羟考酮的尿液样本进行类似分析，可估算人群中超快速代谢者的比例（1.8±1.1%）。肌酐浓度高于 10mg/g 的羟考酮样本显示，亚人群的代谢比值比本研究中的线性预测模型低约 100 倍。本研究描述了尿液中羟考酮和羟吗啡酮的典型范围，并表明可以识别出代谢较快或较慢的个体，他们可能存在不良反应风险。
