Incorporation of Drugs for the Treatment of Substance Abuse into Pigmented and Nonpigmented Hair

Abstract

□ 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 either L-α-acetylmethadol (1 and 3mg/kg; n=6), buprenorphine (1 and 3mg/kg; n=5), or methadone (4 and 8mg/kg; n=5) by intraperitoneal injection daily for 5days. Fourteen days after beginning drug administration, newly grown hair was collected and analyzed for either L-α-acetylmethadol and two metabolites (L-α-acetyl-N-normeth-adol and L-α-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-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 metabolites L-α-acetyl-N-normethadol and D,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, the L-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 high L-α-acetylmethadol dose. These data demonstrate that L-α-acetylmethadol, methadone, buprenorphine, and metabolites are distributed into hair in a dose-related manner with a preference for pigmented hair.