Plasma pharmacokinetics of 3.4-methylenedioxymethamphetamine after controlled oral administration to young adults
Plasma pharmacokinetics of 3.4-methylenedioxymethamphetamine after controlled oral administration to young adults
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DOI：
10.1097/ftd.0b013e3181684fa0
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发表时间：
2008-06-01
影响因子：
2.5
通讯作者：
Huestis, Marilyn A.
中科院分区：
文献类型：
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作者：
Kolbrich, Erin A.;Goodwin, Robert S.;Huestis, Marilyn A.
本研究检查了3，4-亚甲二氧基甲基苯丙胺（MDMA）和代谢产物4-羟基-3-甲氧基甲基苯丙胺（HMMA）、3，4-亚甲二氧基苯丙胺（MDA）和4-羟基-3-甲氧基苯丙胺（HMA）在年轻成人中给药后长达143小时的血浆药代动力学。17名女性和男性受试者（黑人、白色和西班牙裔）在居住于封闭研究单位时，采用双盲、随机、平衡、受试者内设计接受安慰剂、低剂量（1.0 mg/kg）和高剂量（1.6 mg/kg）口服MDMA（与娱乐剂量相当）。给药间隔1周或以上。一个充分验证的二维气相色谱/质谱法同时定量MDMA，HMMA，MDA和HMA。校准曲线为MDA，1 - 100 ng/mL; HMA，2.5 - 100 ng/mL; MDMA和HMMA，2.5 - 400 ng/mL。低剂量MDMA给药后，观察到MDMA和HMMA的平均标准差最大血浆浓度（C-max）分别为162.9 +/- 39.8和171.9 +/- 79.5 ng/mL。高剂量给药后，平均MDMA C-max显著增加至291.8 +/- 76.5 ng/mL，而平均HMMA C-max保持不变，为173.5 +/- 66.3 ng/mL。观察到C-max的受试者间变异性较高。平均MDA C-max为8.4 +/- 2.1（低）和13.8 +/- 3.8（高）ng/mL。低剂量和高剂量给药后，HMA C-max分别为3.5 +/- 0.4和3.9 +/- 0.9 ng/mL。AUC（无穷大）显示出与C-max相似的趋势，证明了非线性药代动力学。末次血浆检测时间一般为HMA < MDA < MDMA < HMMA。MDMA、MDA和HMMA的平均半衰期（t（1/2））分别约为7 - 8小时、10.5 - 12.5小时和11.5 - 13.5小时。HMA t（1/2）变异性高。低剂量和高剂量的平均MDMA分布容积恒定;低剂量后清除率显著升高。本研究首次提供了黑人和女性的MDMA血浆药代动力学数据，以及低剂量和高剂量MDMA给药后的HMMA和HMA浓度测量结果，以及比既往研究更频繁和更长时间的血浆采样。
This study examines the plasma pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA) and metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4-methylene-dioxyamphetamine (MDA), and 4-hydroxy-3-methoxyamphetamine (HMA) in young adults for up to 143 hours after drug administration. Seventeen female and male participants (black, white, and Hispanic) received placebo, low (1.0 mg/kg), and high (1.6 mg/kg) oral MDMA doses (comparable to recreational doses) in a double-blind, randomized, balanced, within-subject design while residing on a closed research unit. Doses were separated by 1 week or more. A fully validated two-dimensional gas chromatography/mass spectrometry method simultaneously quantified MDMA, HMMA, MDA, and HMA. Calibration curves were MDA, 1 to 100 ng/mL; HMA, 2.5 to 100 ng/mL; and MDMA and HMMA, 2.5 to 400 ng/mL. Mean standard deviation maximum plasma concentrations (C-max) of 162.9 +/- 39.8 and 171.9 +/- 79.5 ng/mL were observed for MDMA and HMMA, respectively, after low-dose MDMA. After the high dose, mean MDMA C-max significantly increased to 291.8 +/- 76.5 ng/mL, whereas mean HMMA C-max was unchanged at 173.5 +/- 66.3 ng/mL. High intersubject variability in C-max was observed. Mean MDA C-max were 8.4 +/- 2.1 (low) and 13.8 +/- 3.8 (high) ng/mL. HMA C-max were 3.5 +/- 0.4 and 3.9 +/- 0.9 ng/mL after the low and high doses, respectively. AUC(infinity) displayed similar trends to C-max demonstrating nonlinear pharmacokinetics. Times of last plasma detection were generally HMA < MDA < MDMA < HMMA. Mean half-lives (t(1/2)) of MDMA, MDA, and HMMA were approximately 7 to 8 hours, 10.5 to 12.5 hours, and 11.5 to 13.5 hours, respectively. HMA t(1/2) showed high variability. Mean MDMA volume of distribution was constant for low and high doses; clearance was significantly higher after the low dose. This study presents MDMA plasma pharmacokinetic data for the first time from blacks and females as well as measurement of HMMA and HMA concentrations after low and high MDMA doses and more frequent and extended plasma sampling than in prior studies.