Preston Kenzie L, Epstein David H, Cone Edward J, Wtsadik Abraham T, Huestis Marilyn A, Moolchan Eric T
Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA.
J Anal Toxicol. 2002 Oct;26(7):393-400. doi: 10.1093/jat/26.7.393.
We previously showed that chronic cocaine use by active illicit users produced a longer plasma half-life than expected based on acute low-dose cocaine studies. Here we report urinary excretion patterns of cocaine metabolites as benzoylecgonine (BE) equivalents from 18 of the same individuals, housed for up to 14 days on a closed research unit. In addition, we evaluated whether creatinine normalization of BE equivalents increased mean detection time and reduced mean within-subject variability. All urine voids (N = 953) were individually assayed; BE equivalents were determined semi-quantitatively by FPIA. Compared to concentration in first void after admission, BE equivalents decreased to approximately 33%, 8%, and 4% at 24, 48, and 72 h, respectively. Mean +/- SD (range) time to first negative specimen (BE equivalents < 300 ng/mL) was 43.6 +/- 17.1 (16-66) h. BE equivalents fluctuated considerably across successive specimens; 69% of participants tested positive at least once after testing negative, and the mean time to last positive specimen was 57.5 +/- 31.6 (11-147) h after the first specimen. Thus, mean cocaine metabolite detection times were consistent with prolonged elimination, with 63% of participants testing positive longer than the expected 48-h window of detection after admission to the unit. Mean time to last positive after last use of cocaine, known by self-report only, was approximately 81 +/- 34 (34-162) h. Creatinine normalization, with the cut-off of 300 ng BE equivalents/mg creatinine, increased detection time: mean time to first negative specimen was 54.8 +/- 20.7 (20-100) h, and mean time to last positive specimen was 88.4 +/- 51.0 (35.6-235) h. Compared with the concentration in the first void after admission, BE equivalents/creatinine decreased to approximately 56%, 6%, and 5% at 24, 48, and 72 h. However, creatinine normalization did not reduce the fluctuation of BE equivalents across successive specimens. Thus, creatinine normalized values may be useful when the goal is to maximize the probability or duration of cocaine metabolite detection, but may be less useful in determining whether an individual has used cocaine since a previous specimen collection.
我们之前的研究表明，与基于急性低剂量可卡因研究预期的情况相比，活跃的非法使用者长期使用可卡因会使其血浆半衰期更长。在此，我们报告了来自同一18名个体的可卡因代谢物作为苯甲酰芽子碱（BE）当量的尿排泄模式，这些个体在封闭的研究单元中被安置长达14天。此外，我们评估了BE当量的肌酐标准化是否增加了平均检测时间并降低了个体内的平均变异性。对所有排尿（N = 953）进行单独检测；通过荧光偏振免疫分析（FPIA）半定量测定BE当量。与入院后首次排尿时的浓度相比，BE当量在24、48和72小时时分别降至约33%、8%和4%。首次阴性标本（BE当量<300 ng/mL）的平均±标准差（范围）时间为43.6±17.1（16 - 66）小时。BE当量在连续标本中波动很大；69%的参与者在检测为阴性后至少有一次检测呈阳性，首次标本后最后一次阳性标本的平均时间为57.5±31.6（11 - 147）小时。因此，可卡因代谢物的平均检测时间与消除时间延长一致，63%的参与者检测呈阳性的时间超过了入院后预期的48小时检测窗口期。仅通过自我报告得知的最后一次使用可卡因后到最后一次阳性的平均时间约为81±34（34 - 162）小时。肌酐标准化（截断值为300 ng BE当量/mg肌酐）增加了检测时间：首次阴性标本的平均时间为54.8±20.7（20 - 100）小时，最后一次阳性标本的平均时间为88.4±51.0（35.6 - 235）小时。与入院后首次排尿时的浓度相比，BE当量/肌酐在24、48和72小时时分别降至约56%、6%和%。然而，肌酐标准化并未减少BE当量在连续标本中的波动。因此，当目标是最大化可卡因代谢物检测的概率或持续时间时，肌酐标准化值可能有用，但在确定自上次标本采集以来个体是否使用过可卡因方面可能用处较小。
