Disposition of codeine in female human hair after multiple-dose administration

Studies of the disposition of codeine into the hair of female subjects (n = 7) were performed after a multiple-dose protocol. Caucasian female subjects with dark-brown-to-black hair were administered a total dose of 450 mg codeine over 5 days (30 mg was administered three times a day for 5 days). Analyses of codeine and metabolites in plasma, urine, and hair were performed by positive ion chemical ionization gas chromatography-mass spectrometry (GC-MS) on a Finnigan Magnum" mass spectrometer. Hair was plucked from the scalp for 5 weeks and subsequently cut from the scalp for up to 10 weeks. Prior to analysis, plucked hair specimens were cut into three segments: (a) a proximal, 1-cm segment, which contained the root, (b) the next distal, 3-cm segment, which was closest to the scalp, and (c) a segment containing all remaining hair to the natural hair tip. in female subjects, the mean (plus or minus standard error of the mean) hair concentration of codeine in the proximal, 1-cm segment from plucked hair was 2.7 ng/mg (+/- 0.55) at 12 h after the last codeine dose; 0.44 ng/mg (+/- 0.20) still remained in this segment at 5 weeks. Codeine was detected in the next 3-cm hair segment (above the scalp) at 1 week; the average codeine concentration for 10 weeks in the 3-cm, distal segment was 0.54 ng/mg (+/- O.05). No codeine was detected in the remaining hair segment (to the tip) at any time. In male subjects studied previously, the mean hair concentration of codeine in the proximal, 1-cm hair segment was 2.6 ng/mg (+/- 0.34) at 12 h after the last codeine dose, and no codeine was detected at 5 weeks. Codeine was not detected in the next 3-cm hair segment (above the scalp) until 3 weeks, and the average mean codeine concentration for 10 weeks was 0.09 ng/mg (+/- 0.01). Differences noted between male and female subjects in distal codeine hair concentrations were not explained by plasma pharmacokinetics.