Disposition of methamphetamine and its metabolite amphetamine in brain and other tissues in rats after intravenous administration.
Disposition of methamphetamine and its metabolite amphetamine in brain and other tissues in rats after intravenous administration.
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发表时间：
2000-03
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通讯作者：
G. Rivière;W. Gentry;S. Owens
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作者：
G. Rivière;W. Gentry;S. Owens
这些研究描述了（+）-甲基苯丙胺给药后（+）-甲基苯丙胺[（+）-甲基]及其代谢物（+）-苯丙胺[（+）-AMP]在脑和其他5种组织中的浓度-时间曲线。雄性Sprague-Dawley大鼠接受具有抗肿瘤活性的（+）-METH静脉内推注剂量（1.0 mg/kg）或无抗肿瘤活性的皮下注射剂量（1.0 mg/kg）。输注（1.2 mg/kg/天，20 h）。在i. v.组中采集超过4个消除半衰期的组织（每个时间点n = 3），或在s.c.组中采集单个稳态时间点（20 h）的组织。组根据静脉给药后浓度-时间曲线下面积的数据，（+）-METH组织蓄积的等级顺序为肾脏>脾脏>脑>肝脏>心脏>血清，终末消除半衰期值范围为53 - 66 min。（+）-METH浓度在除脾脏外的所有组织中的第一个测量时间点（2 min）最高，脑-血清浓度比由2 min时的7：1上升到20 min时的13：1，然后平衡到2 h时的恒定值8：1。在s.c.之后在（+）-METH给药后，（+）-METH脑-血清浓度比与静脉内给药后的平衡比相同。（+）-AMP浓度在所有组织中在衰减前20 min达到峰值，终末消除半衰期值范围为68 - 75 min。（+）-AMP和（+）-METH浓度-时间曲线下面积摩尔量分析显示，（+）-AMP约占药物组织暴露量的三分之一。因此，这些数据表明（+）-METH和（+）-AMP在静脉注射（+）-METH后的药理学作用中的重要性。
These studies characterized the concentration-time profile of (+)-methamphetamine [(+)-METH] and its metabolite (+)-amphetamine [(+)-AMP] in the brain and five other tissues after (+)-METH administration. Male Sprague-Dawley rats received a pharmacologically active (+)-METH i.v. bolus dose (1.0 mg/kg) or a nonpharmacologically active s.c. infusion (20 h at 1.2 mg/kg/day). Tissues (n = 3 per time point) were collected for more than four elimination half-lives in the i.v. group, or at a single steady-state time point (20 h) in the s.c. group. Based on data from the area under the concentration-time curves after i.v. dosing, the rank order of (+)-METH tissue accumulation was kidney > spleen > brain > liver > heart > serum with terminal elimination half-life values ranging from 53 to 66 min. (+)-METH concentrations were highest at the first measured time point (2 min) in all tissues except the spleen, which peaked at 10 min. The brain-to-serum concentration ratio rose from 7:1 at 2 min to a peak of 13:1 at 20 min before equilibrating to a constant value of 8:1 at 2 h. Following s.c. (+)-METH dosing, the (+)-METH brain-to-serum concentration ratio was the same as the equilibrated ratio following i.v. dosing. (+)-AMP concentrations peaked at 20 min in all tissues before decaying with terminal elimination half-life values ranging from 68 to 75 min. Analysis of the area under the concentration-time curve molar amounts of (+)-AMP and (+)-METH showed that (+)-AMP accounted for approximately one-third of the drug tissue exposure over time. Thus, these data indicate the importance of both (+)-METH and (+)-AMP in pharmacological effects following i.v. (+)-METH administration.