Codeine disposition in human hair after single and multiple doses

Objective: We studied the dose-proportion and time-course relationships for the incorporation of codeine into human hair after the administration of three different doses. Subjects: Male volunteers, with dark hail; were given oral codeine either as a single dose of 60 mg (n = 7) or 120 mg (n = 12), or as multiple doses of 30 mg 3 times daily for 5 days (n = 7) (450 mg total dose). Methods. Blood and urine were collected for various times for up to 72 h after dosing. Scalp hair was collected initially by plucking (up to 4 weeks) and later by cutting for up to 10 weeks. Plasma, urine, proximal 1 cm of hair and distal hair were each analyzed for codeine and its metabolites by positive-ion chemical ionization ion trap gas chromatography/mass spectrometry. Results: Codeine was detected in the proximal 1 cm of hair within 30 min of an oral 120-mg dose. Codeine was not detected in the distal hair segment until 3 weeks after receiving a dose of codeine. Codeine was detected in distal hair segments for at least 10 weeks at 30 pg mg(-1) hair following a single 120 mg codeine dose and at 90 pg mg(-1) hair following 30 mg codeine 3 times a day for 5 days. Morphine or the glucuronides of codeine or morphine were not detected in the hair specimens of these subjects. Conclusion: Codeine is rapidly distributed into the germanitive elements of hair in a dose-proportional manner. A portion of the codeine remains bound as the hair grows and can be detected in distal hair for up to 10 weeks after a single dose.