Huestis M A, Cone E J
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.
J Anal Toxicol. 1998 Oct;22(6):445-54. doi: 10.1093/jat/22.6.445.
Increases in urine drug concentration that result from changes in urinary output may be mistakenly interpreted as new drug use rather than carryover from previous drug exposure. Normalization of drug excretion to urine creatinine concentration reduces the variability of drug measurement attributable to urine dilution. A specimen ratio of 1.5 or greater between two creatinine normalized positive urine cannabinoid tests was previously proposed as an indicator of new marijuana use. This approach has received wide attention for potential use in treatment and employee assistance programs associated with workplace drug testing. Unfortunately, there has been limited evaluation of the usefulness of this ratio under controlled-dosing conditions with marijuana smokers. A controlled clinical study was conducted to examine the excretion profile of creatinine and marijuana metabolites in a group of six marijuana users who smoked two different doses of marijuana over a 4-week period. A relative operating characteristic curve was constructed from sensitivity and specificity data for 26 different specimen ratios ranging from 0.1 to 2.0. The most accurate specimen ratio (85.4%) for differentiating new use from residual excretion was 0.5. Use of this ratio provided a sensitivity of 80.1%, a specificity of 90.2%, and 5.6% false-positive and 7.4% false-negative predictions. To substantiate the validity of the 0.5 specimen ratio, urine cannabinoid and creatinine data from a controlled clinical trial specifically addressing water dilution as a means of specimen adulteration were evaluated. Sensitivity, specificity, accuracy, and percent false-positive and percent false-negative predictions were 71.9%, 91.6%, 83.9%, 5.4%, and 10.7%, respectively. These data compared favorably with the results from the first clinical study, with the exception of slightly lower sensitivity and higher false-negative percentages in the water dilution study. This would be expected because of the ingestion of large amounts of water and consequent dilution of urine drug concentration. These data indicated that selection of a specimen ratio to evaluate sequential creatinine normalized urine drug concentrations can improve the ability to distinguish residual excretion from new marijuana usage. The selection of an appropriate specimen ratio can be made based on the needs of a specific urine drug-testing program taking into account sensitivity, specificity, and accuracy data.
尿量变化导致的尿液药物浓度升高可能会被错误地解读为新的药物使用，而不是先前药物暴露的残留。将药物排泄量与尿肌酐浓度进行标准化可以减少因尿液稀释导致的药物测量变异性。先前有人提出，两次肌酐标准化的尿大麻素检测结果之间的标本比值为1.5或更高可作为新吸食大麻的指标。这种方法在与工作场所药物检测相关的治疗和员工援助计划中的潜在应用受到了广泛关注。不幸的是，在对大麻吸食者进行控制剂量的条件下，对该比值的实用性评估有限。一项对照临床研究对一组六名大麻使用者进行了研究，这些使用者在4周内吸食了两种不同剂量的大麻，以检查肌酐和大麻代谢物的排泄情况。根据26个不同标本比值（范围从0.1到2.0）的敏感性和特异性数据构建了相对操作特征曲线。区分新使用与残留排泄的最准确标本比值（85.4%）为0.5。使用该比值的敏感性为80.1%，特异性为90.2%，假阳性预测率为5.6%，假阴性预测率为7.4%。为了证实0.5标本比值的有效性，对一项专门针对用水稀释作为标本掺假手段的对照临床试验中的尿大麻素和肌酐数据进行了评估。敏感性、特异性、准确性以及假阳性百分比和假阴性百分比预测分别为71.9%、91.6%、83.9%、5.4%和10.7%。这些数据与第一项临床研究的结果相比具有优势，除了在用水稀释研究中敏感性略低和假阴性百分比略高之外。考虑到大量饮水以及随之而来的尿液药物浓度稀释，这是可以预料的。这些数据表明，选择一个标本比值来评估连续的肌酐标准化尿液药物浓度可以提高区分残留排泄与新吸食大麻的能力。可以根据特定尿液药物检测计划的需求，考虑敏感性、特异性和准确性数据来选择合适的标本比值。
