INCORPORATION OF CODEINE AND METABOLITES INTO HAIR - ROLE OF PIGMENTATION

Xenobiotics circulating in the blood may become incorporated into grow ing hair. Melanin has affinity for many pharmacologically unrelated dr ugs and is responsible for the pigmentation in hair. To assess the rol e of pigmentation in the incorporation of drugs into hair, the distrib ution of codeine and its metabolites was studied in Sprague-Dawley (SD ; white nonpigmented hair), Dark Agouti (DA; brown pigmented hair), an d hooded Long-Evans (LE; both black pigmented and white nonpigmented h air) rats. Codeine was administered at a dose of 40 mg/kg/day ip for 5 days. Fourteen days after beginning the dosing protocol, hair was col lected and analyzed for codeine, and its metabolite, morphine, by posi tive-ion chemical ionization GC/ion-trap MS. The plasma pharmacokineti cs for codeine and morphine were also determined after a single 40 mg/ kg injection (equivalent to first dose in 5-day dosing protocol) in al l three strains of rats. Hair and plasma codeine and morphine concentr ations were also determined after acid hydrolysis to evaluate the pres ence of glucuronide metabolites. Codeine concentrations in the hair of SD, DA, and pigmented LE hair were 0.98 +/- 0.10, 5.99 +/- 1.24, and 111.93 +/- 18.69 ng/mg hair, respectively; morphine concentrations wer e 0.34 +/- 0.04, 0.51 +/- 0.11, and 14.46 +/- 1.81 ng/mg hair, respect ively; morphine glucuronide concentrations were 0.67 +/- 0.08, 1.04 +/ - 0.37, and 13.80 +/- 3.60 ng/mg hair, respectively. Studies examining the in vitro binding of [H-3]codeine and [H-3]morphine to hair demons trated both specific and nonspecific binding sites for codeine and mor phine. Pigmented hair from LE rats possessed the greatest number of bi nding sites, white hair from SD rats contained the least, and brown ha ir from DA rats was intermediate. A time course study of codeine and i ts metabolites showed pigment-mediated differences in incorporation of codeine and metabolites within a few hours of drug administration. Th ese data indicate that pigmented hair possesses a greater capacity to bind and incorporate codeine and its metabolites than does nonpigmente d hair. Interpretation of hair concentrations of drugs should involve consideration of hair pigmentation.