Nakahara Y, Kikura R, Takahashi K
National Institute of Health Sciences, Setagaya, Tokyo, Japan.
Life Sci. 1998;63(10):883-93. doi: 10.1016/s0024-3205(98)00345-2.
To elucidate drug disposition in hair, the incorporation and retention behavior of 7 phenethylamines in the rat hair root were investigated: methamphetamine(MA), 3,4-methylenedioxymethamphetamine(MDMA), benzphetamine(BZP), ephedrine(EP), N,N-dimethylamphetamine(DMA), p-nitro-methamphetamine(NO2MA), and N-acetylmethamphetamine(AcMA). On day 10 after shaving the hair on the back of the rats, drug was intraperitoneally administered at a single dose of 10 mg/kg to Long Evans rats (which were male and 6 weeks of age), possessing black and white hair, and the back hair that grew was collected by plucking with hair nippers at 0.083 h (5 min), 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 9 h, 24 h, 33 h and 48 h. After washing the plucked hairs three times with 0.1% sodium dodecylsulfate, the amount of drug in each of the hair root samples was analyzed by a selected ion monitoring of gas chromatography mass spectrometry (GC-MS) analysis. The times at which the concentration of each drug in the hair root samples reached the peak concentration, ranged between 3.30 and 41.51 ng/mg. For each drug, the point of time at which the largest positive incremental change in drug concentration was seen, ranged between 5 min and 1 h, for all of the drugs except for AcMA which was hardly incorporated in the rat hair. The data showed that there are mainly 4 modes in which a drug becomes incorporated into the black hair root: rapid and prolonged incorporation (NO2MA, MDMA), rapid and short incorporation(MA, DMA), slow and prolonged incorporation(BZP, EP), slow and short incorporation, which includes hardly any incorporation (AcMA). As all seven drugs were hardly incorporated into the white hair, it was concluded that the combination of melanin and basic compounds is essential for a drug to become incorporated into hair. Our results suggest that a portion of the drugs in the hair root is accumulated in the hair shaft, and the remaining portion is redistributed outside the hair shaft. The second finding is that the concentration of drug incorporated into hair mainly depends on two processes--(1) the drug incorporation into hair and the drug retention in hair.
为阐明药物在毛发中的分布情况，研究了7种苯乙胺在大鼠毛根中的掺入和保留行为：甲基苯丙胺（MA）、3,4-亚甲基二氧基甲基苯丙胺（MDMA）、苄非他明（BZP）、麻黄碱（EP）、N,N-二甲基苯丙胺（DMA）、对硝基甲基苯丙胺（NO2MA）和N-乙酰甲基苯丙胺（AcMA）。在剃除大鼠背部毛发后的第10天，以10mg/kg的单剂量对长 Evans 大鼠（雄性，6周龄）进行腹腔注射给药，这些大鼠毛发黑白相间，用拔毛钳在0.083小时（5分钟）、0.25小时、0.5小时、1小时、2小时、4小时、6小时、9小时、24小时、33小时和48小时收集生长出的背部毛发。用0.1%十二烷基硫酸钠将拔下的毛发洗涤三次后，通过气相色谱-质谱联用仪（GC-MS）的选择离子监测分析每个毛根样品中的药物含量。毛根样品中每种药物浓度达到峰值浓度的时间在3.30至41.51 ng/mg之间。对于每种药物，除几乎不掺入大鼠毛发的AcMA外，药物浓度出现最大正向增量变化的时间点在5分钟至1小时之间。数据表明，药物掺入黑色毛根主要有4种模式：快速且持续掺入（NO2MA、MDMA）、快速且短暂掺入（MA、DMA）、缓慢且持续掺入（BZP、EP）、缓慢且短暂掺入（包括几乎不掺入，AcMA）。由于所有7种药物几乎都不掺入白色毛发，因此得出结论，黑色素与碱性化合物的结合是药物掺入毛发所必需的。我们的结果表明，毛根中的一部分药物积聚在毛干中，其余部分重新分布到毛干外。第二个发现是，掺入毛发中的药物浓度主要取决于两个过程——（1）药物掺入毛发和药物在毛发中的保留。
