Montefiore Medical Center, Bronx, NY, USA.
Weill-Cornell Pain Medicine Center and New York Presbyterian Hospital, New York, NY, USA.
Pain Med. 2017 Nov 1;18(11):2162-2169. doi: 10.1093/pm/pnw335.
Interpretation limitations of urine drug testing and the invasiveness of blood toxicology have motivated the desire for the development of simpler methods to assess biologically active drug levels on an individualized patient basis. Oral fluid is a matrix well-suited for the challenge because collections are based on simple noninvasive procedures and drug concentrations better correlate to blood drug levels as oral fluid is a filtrate of the blood. Well-established pharmacokinetic models were utilized to generate oral fluid steady state concentration ranges to assess the interpretive value of the alternative matrix to monitor steady state plasma oxycodone levels.
Paired oral fluid and plasma samples were collected from patients chronically prescribed oxycodone and quantitatively analyzed by liquid chromatography tandem mass spectrometry. Steady state plasma concentration ranges were calculated for each donor and converted to an equivalent range in oral fluid. Measured plasma and oral fluid oxycodone concentrations were compared with respective matrix-matched steady state ranges, using each plasma steady state classification as the control.
A high degree of correlation was observed between matrices when classifying donors according to expected steady state oxycodone concentration. Agreement between plasma and oral fluid steady state classifications was observed in 75.6% of paired samples. This study supports novel application of basic pharmacokinetic knowledge to the pain management industry, simplifying and improving individualized drug monitoring and risk assessment through the use of oral fluid drug testing. Many benefits of established therapeutic drug monitoring in plasma can be realized in oral fluid for patients chronically prescribed oxycodone at steady state.
尿液药物检测的解释局限性和血液毒理学的侵入性促使人们希望开发更简单的方法，以便根据个体患者的情况评估生物活性药物水平。口腔液是一种非常适合这一挑战的基质，因为采集过程基于简单的非侵入性程序，而且药物浓度与血液药物水平的相关性更好，因为口腔液是血液的滤出物。本研究利用成熟的药代动力学模型来生成口腔液稳态浓度范围，以评估替代基质监测稳态血浆羟考酮水平的解释价值。
从长期服用羟考酮的患者中采集配对的口腔液和血浆样本，并通过液相色谱串联质谱法进行定量分析。为每个供体计算稳态血浆浓度范围，并转换为口腔液中的等效范围。将测量的血浆和口腔液羟考酮浓度与各自基质匹配的稳态范围进行比较，以每个血浆稳态分类作为对照。
当根据预期稳态羟考酮浓度对供体进行分类时，两种基质之间观察到高度相关性。在 75.6%的配对样本中观察到血浆和口腔液稳态分类之间的一致性。这项研究支持将基本药代动力学知识应用于疼痛管理行业，通过使用口腔液药物检测简化和改进个体化药物监测和风险评估。对于长期服用羟考酮处于稳态的患者，许多在血浆中进行的既定治疗药物监测的优势可以在口腔液中实现。
