Wilkins D G, Valdez A S, Nagasawa P R, Gygi S P, Rollins D E
Center for Human Toxicology, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112, USA.
J Pharm Sci. 1998 Apr;87(4):435-40. doi: 10.1021/js970360t.
Hair analysis for drugs may be useful for the long-term monitoring of recidivism and treatment compliance. L-alpha-Acetylmethadol, 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 either L-alpha-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 either L-alpha-acetylmethadol and two metabolites (L-alpha-acetyl-N-normethadol and L-alpha-acetyl-N,N-dinormethadol), methadone and two metabolites (D,L-2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium and D,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 of L-alpha-acetylmethadol, methadone, and buprenorphine in nonpigmented hair were significantly less than that measured in pigmented hair at either the high or low dose. The metabolites L-alpha-acetyl-N-normethadol and D,L-2-ethyl-1,5dimethyl-3,3-diphenylpyrrolinium were detected at lower concentrations than their respective parent compounds (L-alpha-acetylmethadol or methadone) in pigmented hair. However, the L-alpha-acetyl-N,N-dinormethadol metabolite concentrations in pigmented hair were significantly greater than those of the parent drug after either the low or the high L-alpha-acetylmethadol dose. These data demonstrate that L-alpha-acetylmethadol, methadone, buprenorphine, and metabolites are distributed into hair in a dose-related manner with a preference for pigmented hair.
药物毛发分析对于复吸和治疗依从性的长期监测可能有用。L-α-乙酰美沙酮、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大鼠每天腹腔注射L-α-乙酰美沙酮（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），持续5天。开始给药14天后，收集新长出的毛发，并分析其中的L-α-乙酰美沙酮及其两种代谢物（L-α-乙酰-N-去甲美沙酮和L-α-乙酰-N,N-二去甲美沙酮）、美沙酮及其两种代谢物（D,L-2-乙基-1,5-二甲基-3,3-二苯基吡咯鎓和D,L-2-乙基-5-甲基-3,3-二苯基-1-吡咯啉）或丁丙诺啡及其一种代谢物（去甲丁丙诺啡）。在以指定剂量单次给药每种药物后，还测定了每种化合物的血浆时间进程（AUC）。在有色毛发中，每种母体药物的测量毛发浓度大致呈剂量依赖性增加。在高剂量或低剂量下，无色毛发中L-α-乙酰美沙酮、美沙酮和丁丙诺啡的浓度均显著低于有色毛发中的测量浓度。在有色毛发中，代谢物L-α-乙酰-N-去甲美沙酮和D,L-2-乙基-1,5-二甲基-3,3-二苯基吡咯鎓的检测浓度低于各自的母体化合物（L-α-乙酰美沙酮或美沙酮）。然而，在低剂量或高剂量的L-α-乙酰美沙酮给药后，有色毛发中L-α-乙酰-N,N-二去甲美沙酮代谢物的浓度显著高于母体药物。这些数据表明，L-α-乙酰美沙酮、美沙酮、丁丙诺啡及其代谢物以剂量相关的方式分布到毛发中，且更倾向于有色毛发。
