INCORPORATION OF DRUGS FOR THE TREATMENT OF SUBSTANCE-ABUSE INTO PIGMENTED AND NONPIGMENTED HAIR

Citation
Dg. Wilkins et al., INCORPORATION OF DRUGS FOR THE TREATMENT OF SUBSTANCE-ABUSE INTO PIGMENTED AND NONPIGMENTED HAIR, Journal of pharmaceutical sciences, 87(4), 1998, pp. 435-440
Citations number
63
Categorie Soggetti
Chemistry Medicinal","Pharmacology & Pharmacy
ISSN journal
00223549
Volume
87
Issue
4
Year of publication
1998
Pages
435 - 440
Database
ISI
SICI code
0022-3549(1998)87:4<435:IODFTT>2.0.ZU;2-E
Abstract
Hair analysis for drugs may be useful for the long-term monitoring of recidivism and treatment compliance. L-alpha-Acetylmethadol, buprenorp hine, and methadone are drugs that are used for the treatment of subst ance abuse. The purpose of this study was to study the relationship be tween dose, plasma concentration, hair concentration, and hair pigment ation for these compounds and their major metabolites in an animal mod el. 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. F ourteen days after beginning drug administration, newly grown hair was collected and analyzed for either L-alpha-acetylmethadol and two meta bolites (L-alpha-acetyl-N-normethadol and L-alpha-acetyl-N,N-dinormeth adol), methadone and two metabolites (D,L-2-ethyl-1,5-dimethyl-3,3-dip henylpyrrolinium and D,L-2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline), o r buprenorphine and one metabolite (norbuprenorphine). The plasma time course (AUG) for each compound was also determined after a single adm inistration of each drug at the specified doses. There was an approxim ate dose-dependent increase in measured hair concentration of each par ent drug in pigmented hair. The concentrations of L-alpha-acetylmethad ol, methadone, and buprenorphine in nonpigmented hair were significant ly 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, 5-dimethyl-3,3-diphenylpyrrolinium were detected at lower concentratio ns than their respective parent compounds (L-alpha-acetylmethadol or m ethadone) in pigmented hair. However, the L-alpha-acetyl-N,N-dinormeth adol metabolite concentrations in pigmented hair were significantly gr eater than those of the parent drug after either the low or the high L -alpha-acetylmethadol dose. These data demonstrate that L-alpha-acetyl methadol, methadone, buprenorphine, and metabolites are distributed in to hair in a dose-related manner with a preference for pigmented hair.