St. Luke's Roosevelt Hospital Center, 324 W. 108th Street, #505, New York, NY 10025, USA.
Drug Alcohol Depend. 2013 Feb 1;128(1-2):77-82. doi: 10.1016/j.drugalcdep.2012.08.007. Epub 2012 Aug 22.
Noncompliance with medications may have major impacts on outcomes measured in research, potentially distorting the validity of controlled clinical trials. Riboflavin is frequently used in trials as a marker of adherence. It can be combined with study medication and is excreted in urine where it fluoresces under UV light. This study compares qualitative visual inspection of fluorescence to quantitative fluorometric analysis of riboflavin concentration in its ability to detect the presence of riboflavin in urine.
Twenty-four volunteers received 0mg, 25mg, and 50mg doses of riboflavin under single-blind conditions, with 20 also receiving a 100mg dose. Five serial urine samples were collected over the following 36h. Quantitative measurement of riboflavin by fluorometric analysis and qualitative assessment of each sample using visual inspection were performed.
The overall false positive rate for qualitative assessment was 53%. For quantitative assessment, a riboflavin concentration of 900ng/mL was established to classify positive samples. More than 80% of samples were positive 2-24h following ingestion of 25mg and 50mg, and less than 80% were positive at 36h. At least 95% of observations for the 100mg dose were above 900ng/mL at all timepoints.
Quantitative fluorometric assessment is superior to qualitative visual inspection alone in determining medication adherence. The combination of 25-50mg of daily riboflavin and a cut-off level of 900ng/mL allows for the acceptable sensitivity of missing detection of non-compliant participants while preserving a high level of power to detect all cases of medication compliance.
不遵守药物治疗可能会对研究中测量的结果产生重大影响，从而潜在地扭曲对照临床试验的有效性。核黄素经常在试验中用作依从性的标志物。它可以与研究药物结合，并在尿液中排泄，在紫外光下会发出荧光。本研究比较了定性荧光目测法和定量荧光光度法分析核黄素浓度检测尿液中核黄素的能力。
24 名志愿者在单盲条件下接受 0mg、25mg 和 50mg 的核黄素剂量，其中 20 名还接受 100mg 剂量。在接下来的 36 小时内收集 5 个连续的尿液样本。通过荧光光度法对核黄素进行定量测量，并使用目测法对每个样本进行定性评估。
定性评估的总体假阳性率为 53%。对于定量评估，建立了 900ng/mL 的核黄素浓度来分类阳性样本。在摄入 25mg 和 50mg 后 2-24 小时，超过 80%的样本呈阳性，而在 36 小时时，不到 80%的样本呈阳性。对于 100mg 剂量，至少 95%的观察结果在所有时间点均高于 900ng/mL。
与单独的定性荧光目测法相比，定量荧光光度法更能准确地确定药物依从性。每日 25-50mg 核黄素与 900ng/mL 截断值的组合可在可接受的灵敏度下检测出不遵守治疗方案的参与者，同时保持高检测所有药物依从性病例的能力。
