Incorporation of drugs for the treatment of substance abuse into pigmented and nonpigmented hair.
Incorporation of drugs for the treatment of substance abuse into pigmented and nonpigmented hair.
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将用于治疗药物滥用的药物掺入有色和无色头发中。
DOI：
10.1021/js970360t
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Rollins,DE
中科院分区：
文献类型：
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作者：
Wilkins,DG;Valdez,AS;Nagasawa,PR;Gygi,SP;Rollins,DE
毛发药物分析可能有助于长期监测复发和治疗依从性。L-α-乙酰甲基-阿朵、丁丙诺啡和美沙酮是用于治疗药物滥用的药物。本研究的目的是在动物模型中研究这些化合物及其主要代谢物的剂量、血浆浓度、毛发浓度和毛发色素沉着之间的关系。雄性Long-Evans大鼠每日腹腔注射L-α-乙酰美沙醇(1和3 mg/kg；n=6)、丁丙诺啡(1和3 mg/kg；n=5)或美沙酮(4和8 mg/kg；n=5)。给药14d后，取新生毛发，分别检测L-L‐2‐ethyl‐1，5‐dimethyl‐3，3‐diphenylpyrrolinium-乙酰美沙醇和两种代谢物(L-α-乙酰基-N-去甲肾上腺素和L-α-乙酰基-N，N-二甲基美沙醇)、美沙酮和两种代谢物(D，α和d，L-2-乙基-5-甲基-3，3-二苯基-1-吡咯烷)和丁丙诺啡和1种代谢物(去丁丙诺啡)。每种化合物的血浆时间进程(AUC)也在每种药物按指定剂量单次给药后被测定。在着色的头发中，每种母体药物的测量毛发浓度都有大致的剂量依赖性增加。无论是高剂量还是低剂量，非色素头发中L-α-乙酰美沙醇、美沙酮和丁丙诺啡的浓度均显著低于色素头发中的浓度。发色毛发中的代谢物L-L‐2‐ethyl‐1，5‐dimethyl‐3，3‐diphenylpyrrolinium和D，α的浓度均低于其母体化合物(L-α-乙酰美沙酮或美沙酮)。然而，无论是低剂量还是高剂量的L-α-乙酰美沙尔，发色毛发中L-α-乙酰基-N，N-二降冰片代谢物的浓度均显著高于母体药物。这些数据表明，L-α-乙酰美沙醇、美沙酮、丁丙诺啡和代谢物以剂量相关的方式分布到头发中，并偏爱有色头发。
Hair analysis for drugs may be useful for the long‐term monitoring of recidivism and treatment compliance.L‐α‐Acetylmeth‐adol, buprenorphine, and methadone are drugs that are used for the treatment of substance abuse. The purpose of this study was to study the relationship between dose, plasma concentration, hair concentration, and hair pigmentation for these compounds and their major metabolites in an animal model. Male Long‐Evans rats received eitherL‐α‐acetylmethadol (1 and 3 mg/kg;n= 6), buprenorphine (1 and 3 mg/kg;n= 5), or methadone (4 and 8 mg/kg;n= 5) by intraperitoneal injection daily for 5 days. Fourteen days after beginning drug administration, newly grown hair was collected and analyzed for eitherL‐α‐acetylmethadol and two metabolites (L‐α‐acetyl‐N‐normeth‐adol andL‐α‐acetyl‐N,N‐dinormethadol), methadone and two metabo‐lites (D,L‐2‐ethyl‐1,5‐dimethyl‐3,3‐diphenylpyrrolinium andD,L‐2‐ethyl‐5‐methyl‐3,3‐diphenyl‐1‐pyrroline), or buprenorphine and one metabolite (norbuprenorphine). The plasma time course (AUC) for each compound was also determined after a single administration of each drug at the specified doses. There was an approximate dose‐dependent increase in measured hair concentration of each parent drug in pigmented hair. The concentrations ofL‐α‐acetylmethadol, methadone, and buprenorphine in nonpigmented hair were significantly less than that measured in pigmented hair at either the high or low dose. The metabolitesL‐α‐acetyl‐N‐normethadol andD,L‐2‐ethyl‐1,5‐dimethyl‐3,3‐diphenylpyrrolinium were detected at lower concentrations than their respective parent compounds (L‐α‐acetylmethadol or methadone) in pigmented hair. However, theL‐α‐acetyl‐N,N‐di‐normethadol metabolite concentrations in pigmented hair were significantly greater than those of the parent drug after either the low or the highL‐α‐acetylmethadol dose. These data demonstrate thatL‐α‐acetylmethadol, methadone, buprenorphine, and metabolites are distributed into hair in a dose‐related manner with a preference for pigmented hair.