Lee Dayong, Vandrey Ryan, Milman Garry, Bergamaschi Mateus, Mendu Damodara R, Murray Jeannie A, Barnes Allan J, Huestis Marilyn A
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Biomedical Research Center, Baltimore, MD 21224, USA.
Anal Bioanal Chem. 2013 Sep;405(23):7269-79. doi: 10.1007/s00216-013-7159-8. Epub 2013 Jul 6.
Oral fluid (OF) is a valuable biological alternative for clinical and forensic drug testing. Evaluating OF to plasma (OF/P) cannabinoid ratios provides important pharmacokinetic data on the disposition of drug and factors influencing partition between matrices. Eleven chronic cannabis smokers resided on a closed research unit for 51 days. There were four 5-day sessions of 0, 30, 60, and 120 mg oral ∆(9)-tetrahydrocannabinol (THC)/day followed by a five-puff smoked cannabis challenge on Day 5. Each session was separated by 9 days ad libitum cannabis smoking. OF and plasma specimens were analyzed for THC and metabolites. During ad libitum smoking, OF/P THC ratios were high (median, 6.1; range, 0.2-348.5) within 1 h after last smoking, decreasing to 0.1-20.7 (median, 2.1) by 13.0-17.1 h. OF/P THC ratios also decreased during 5-days oral THC dosing, and after the smoked cannabis challenge, median OF/P THC ratios decreased from 1.4 to 5.5 (0.04-245.6) at 0.25 h to 0.12 to 0.17 (0.04-5.1) at 10.5 h post-smoking. In other studies, longer exposure to more potent cannabis smoke and oromucosal cannabis spray was associated with increased OF/P THC peak ratios. Median OF/P 11-nor-9-carboxy-THC (THCCOOH) ratios were 0.3-2.5 (range, 0.1-14.7) ng/μg, much more consistent in various dosing conditions over time. OF/P THC, but not THCCOOH, ratios were significantly influenced by oral cavity contamination after smoking or oromucosal spray of cannabinoid products, followed by time-dependent decreases. Establishing relationships between OF and plasma cannabinoid concentrations is essential for making inferences of impairment or other clinical outcomes from OF concentrations.
口腔液（OF）是临床和法医药物检测中一种有价值的生物替代样本。评估口腔液与血浆（OF/P）中大麻素的比例可提供有关药物处置以及影响基质间分配的因素的重要药代动力学数据。11名慢性大麻吸烟者在一个封闭的研究单位居住了51天。有四个为期5天的阶段，每天分别服用0、30、60和120毫克口服Δ⁹ - 四氢大麻酚（THC），然后在第5天进行五次吸食大麻的挑战。每个阶段之间间隔9天的随意吸食大麻时间。对口腔液和血浆样本进行了THC及其代谢物分析。在随意吸食期间，最后一次吸烟后1小时内，OF/P THC比例较高（中位数为6.1；范围为0.2 - 348.5），到13.0 - 17.1小时时降至0.1 - 20.7（中位数为2.1）。在为期5天的口服THC给药期间以及吸食大麻挑战后，OF/P THC比例也有所下降，吸食后0.25小时时，OF/P THC比例中位数从1.4降至5.5（0.04 - 245.6），到10.5小时时降至0.12至0.17（0.04 - 5.1）。在其他研究中，更长时间接触更强效的大麻烟雾和口腔黏膜大麻喷雾剂与OF/P THC峰值比例增加有关。OF/P 11 - 去甲 - 9 - 羧基 - THC（THCCOOH）比例中位数为0.3 - 2.5（范围为0.1 - 14.7）纳克/微克，在不同给药条件下随时间变化更为一致。吸烟或口腔黏膜喷洒大麻素产品后，口腔污染会显著影响OF/P THC比例，但不影响THCCOOH比例，随后比例会随时间下降。建立口腔液和血浆大麻素浓度之间的关系对于根据口腔液浓度推断损伤或其他临床结果至关重要。
