Δ9-Tetrahydrocannabinol (THC), 11-Hydroxy-THC, and 11-Nor-9-carboxy-THC Plasma Pharmacokinetics during and after Continuous High-Dose Oral THC
Δ9-Tetrahydrocannabinol (THC), 11-Hydroxy-THC, and 11-Nor-9-carboxy-THC Plasma Pharmacokinetics during and after Continuous High-Dose Oral THC
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DOI：
10.1373/clinchem.2008.122119
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发表时间：
2009-12-01
影响因子：
9.3
通讯作者：
Huestis, Marilyn A.
中科院分区：
文献类型：
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作者：
Schwilke, Eugene W.;Schwope, David M.;Huestis, Marilyn A.
背景技术背景：Delta（9）-Tetrahydrocannabinol（THC）是大麻的主要精神活性成分，也是一种活性大麻素药物治疗成分。没有血浆药代动力学数据后，反复口服THC administrations.METHODS：六个成年男性每日大麻吸烟者居住在一个封闭的临床研究单位。口服THC胶囊（20 mg）每4-8小时给药一次，每日总剂量递增（40-120 mg），持续7天。游离和葡萄糖醛酸化血浆THC，11-羟基-THC（11-OH-THC）和11-去甲-9-羧基-THC在给药期间和给药后，通过二维GC-MS定量（THC COOH）。入院后19.5 h血浆游离THC、11-OH-THC和THC-COOH浓度（对照口服THC给药前）分别为平均4.3（SE 1.1）、1.3（0.5）和34.0（8.4）μ g/L。在口服给药期间，游离11-OH-THC和THCCOOH稳定增加，而THC则没有。末次给药后22.5 h，平均血浆游离THC、11-OH-THC和THCCOOH浓度峰值分别为3.8（0.5）、3.0（0.7）和196.9（39.9）μ g/L。大肠杆菌P-葡萄糖醛酸酶水解264大麻素标本产生统计学显着增加THC，11-OH-THC，和THCCOOH浓度（P < 0.001），但共轭浓度被低估，由于不完全酶水解。结论：血浆THC浓度保持> 1 μ g/L至少1天后，每天吸食大麻，也停止多次口服THC剂量。我们首次报告了在白天和晚上多次高剂量口服THC后以及大肠杆菌β-葡萄糖醛酸酶水解后的游离血浆THC浓度。这些数据将有助于解释多次口服剂量后的血浆THC浓度。(C)2009年美国临床化学协会
BACKGROUND: Delta(9)-Tetrahydrocannabinol (THC) is the primary psychoactive constituent of cannabis and an active cannabinoid pharmacotherapy component. No plasma pharmacokinetic data after repeated oral THC administration are available.METHODS: Six adult male daily cannabis smokers resided on a closed clinical research unit. Oral THC capsules (20 mg) were administered every 4-8 h in escalating total daily doses (40-120 mg) for 7 days. Free and glucuronidated plasma THC, 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THC COOH) were quantified by 2-dimensional GC-MS during and after dosing.RESULTS: Free plasma THC, 11-OH-THC, and THC-COOH concentrations 19.5 h after admission (before controlled oral THC dosing) were mean 4.3 (SE 1.1), 1.3 (0.5), and 34.0 (8.4) mu g/L, respectively. During oral dosing, free 11-OH-THC and THCCOOH increased steadily, whereas THC did not. Mean peak plasma free THC, 11-OH-THC, and THCCOOH concentrations were 3.8 (0.5), 3.0 (0.7), and 196.9 (39.9) mu g/L, respectively, 22.5 h after the last dose. Escherichia coli P-glucuronidase hydrolysis of 264 cannabinoid specimens yielded statistically significant increases in THC, 11-OH-THC, and THCCOOH concentrations (P < 0.001), but conjugated concentrations were underestimated owing to incomplete enzymatic hydrolysis.CONCLUSIONS: Plasma THC concentrations remained > 1 mu g/L for at least 1 day after daily cannabis smoking and also after cessation of multiple oral THC doses. We report for the first time free plasma THC concentrations after multiple high-dose oral THC throughout the day and night, and after Escherichia coli beta-glucuronidase hydrolysis. These data will aid in the interpretation of plasma THC concentrations after multiple oral doses. (C) 2009 American Association for Clinical Chemistry