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
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.