Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications.
Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications.
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DOI：
10.1371/journal.pone.0015269
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发表时间：
2010-12-07
期刊：
影响因子：
3.7
通讯作者：
Alexoff D
中科院分区：
文献类型：
--
作者：
Volkow ND;Fowler JS;Wang GJ;Shumay E;Telang F;Thanos PK;Alexoff D
甲基苯丙胺是滥用药物中毒性最大的药物之一，这可能反映了其在体内的分布和积累。然而，没有研究测量甲基苯丙胺在人体内的器官分布。正电子发射断层扫描（PET）与[11C]d-甲基苯丙胺结合使用，通过健康参与者（9名白种人和10名非洲裔美国人）的峰值摄取（%剂量/cc）、清除率（达到50%峰值清除率的时间）和积累（曲线下面积）来评估其全身分布和生物利用度。甲基苯丙胺分布于大多数器官。最高的（全器官）摄取发生在肺部（22%剂量；体重~ 1246 g），肝脏（23%剂量；体重~ 1677 g）和脑部（10%剂量；体重~ 1600 g）。肾脏也显示高摄取（每毫升）（7%；体重305克）。甲基苯丙胺在心脏和肺部的清除率最高（7 ~ 16分钟），在脑、肝和胃的清除率最低（约75分钟），在肾、脾和胰腺的清除率居中（22 ~ 50分钟）。非裔美国人肺中[11C]d-甲基苯丙胺的蓄积量比白种人高30% (p<0.05)，但在其他器官中无差异。甲基苯丙胺是一种强效兴奋剂，在大多数身体器官中大量积累，很可能导致与甲基苯丙胺滥用有关的医疗并发症。特别是，我们推测甲基苯丙胺的高肺摄取可能使这个器官容易感染（肺结核）和病理（肺动脉高压）。我们初步发现非裔美国人的甲基苯丙胺肺积累量高于白种人，值得进一步调查，并质疑这是否可能导致非裔美国人很少使用甲基苯丙胺。
Methamphetamine is one of the most toxic of the drugs of abuse, which may reflect its distribution and accumulation in the body. However no studies have measured methamphetamine's organ distribution in the human body. Positron Emission Tomography (PET) was used in conjunction with [11C]d-methamphetamine to measure its whole-body distribution and bioavailability as assessed by peak uptake (% Dose/cc), rate of clearance (time to reach 50% peak-clearance) and accumulation (area under the curve) in healthy participants (9 Caucasians and 10 African Americans). Methamphetamine distributed through most organs. Highest uptake (whole organ) occurred in lungs (22% Dose; weight ∼1246 g), liver (23%; weight ∼1677 g) and intermediate in brain (10%; weight ∼1600 g). Kidneys also showed high uptake (per/cc basis) (7%; weight 305 g). Methamphetamine's clearance was fastest in heart and lungs (7–16 minutes), slowest in brain, liver and stomach (>75 minutes), and intermediate in kidneys, spleen and pancreas (22–50 minutes). Lung accumulation of [11C]d-methamphetamine was 30% higher for African Americans than Caucasians (p<0.05) but did not differ in other organs. The high accumulation of methamphetamine, a potent stimulant drug, in most body organs is likely to contribute to the medical complications associated with methamphetamine abuse. In particular, we speculate that methamphetamine's high pulmonary uptake could render this organ vulnerable to infections (tuberculosis) and pathology (pulmonary hypertension). Our preliminary findings of a higher lung accumulation of methamphetamine in African Americans than Caucasians merits further investigation and questions whether it could contribute to the infrequent use of methamphetamine among African Americans.
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