| Popis: |
Xenobiotics circulating in the blood may become incorporated into growing hair. Melanin has affinity for many pharmacologically unrelated drugs and is responsible for the pigmentation in hair. To assess the role of pigmentation in the incorporation of drugs into hair, the distribution of codeine and its metabolites was studied in Sprague-Dawley (SD; white nonpigmented hair), Dark Agouti (DA; brown pigmented hair), and hooded Long-Evans (LE; both black pigmented and white nonpigmented hair) rats. Codeine was administered at a dose of 40 mg/kg/day i.p. for 5 days. Fourteen days after beginning the dosing protocol, hair was collected and analyzed for codeine, and its metabolite, morphine, by positive-ion chemical ionization GC/ion-trap MS. The plasma pharmacokinetics for codeine and morphine were also determined after a single 40 mg/kg injection (equivalent to first dose in 5-day dosing protocol) in all three strains of rats. Hair and plasma codeine and morphine concentrations were also determined after acid hydrolysis to evaluate the presence 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 were 0.34 +/- 0.04, 0.51 +/- 0.11, and 14.46 +/- 1.81 ng/mg hair, respectively; 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 [3H] codeine and [3H]morphine to hair demonstrated both specific and nonspecific binding sites for codeine and morphine. Pigmented hair from LE rats possessed the greatest number of binding sites, white hair from SD rats contained the least, and brown hair from DA rats was intermediate. A time course study of codeine and its metabolites showed pigment-mediated differences in incorporation of codeine and metabolites within a few hours of drug administration. These data indicate that pigmented hair possesses a greater capacity to bind and incorporate codeine and its metabolites than does nonpigmented hair. Interpretation of hair concentrations of drugs should involve consideration of hair pigmentation. |
