Incorporation of codeine and metabolites into hair. Role of pigmentation.
Incorporation of codeine and metabolites into hair. Role of pigmentation.
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发表时间：
1996-04
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通讯作者：
S. Gygi;R. Joseph;E. Cone;D. Wilkins;D. Rollins
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作者：
S. Gygi;R. Joseph;E. Cone;D. Wilkins;D. Rollins
血液中循环的异生物质可能会融入正在生长的毛发中。黑色素对许多药理学上不相关的药物具有亲和力，并且是头发色素沉着的原因。为了评估色素沉着在药物掺入头发中的作用，在 Sprague-Dawley（SD；白色无色素毛发）、Dark Agouti（DA；棕色色素毛发）和 hooded Long-Evans（LE；黑色色素和白色无色素毛发）大鼠中研究了可待因及其代谢物的分布。可待因的剂量为 40 mg/kg/天，腹腔注射。 5天。开始给药方案14天后，收集头发并通过正离子化学电离GC/离子阱MS分析可待因及其代谢物吗啡。还在所有三种品系的大鼠中单次注射 40 mg/kg（相当于 5 天给药方案中的第一剂）后测定了可待因和吗啡的血浆药代动力学。酸水解后还测定了头发和血浆可待因和吗啡浓度，以评估葡萄糖醛酸代谢物的存在。 SD、DA 和色素 LE 头发中的可待因浓度分别为 0.98 +/- 0.10、5.99 +/- 1.24 和 111.93 +/- 18.69 ng/mg 头发；吗啡浓度分别为 0.34 +/- 0.04、0.51 +/- 0.11 和 14.46 +/- 1.81 ng/mg 头发；吗啡葡萄糖醛酸浓度分别为0.67 +/- 0.08、1.04 +/- 0.37 和13.80 +/- 3.60 ng/mg 头发。检查[3H]可待因和[3H]吗啡与头发的体外结合的研究证明了可待因和吗啡的特异性和非特异性结合位点。 LE 大鼠的色素毛发拥有最多的结合位点，SD 大鼠的白发包含最少的结合位点，而 DA 大鼠的棕色毛发则居中。可待因及其代谢物的时程研究表明，在给药后几个小时内，可待因及其代谢物的掺入存在色素介导的差异。这些数据表明，有色头发比无色头发具有更大的结合和掺入可待因及其代谢物的能力。头发药物浓度的解释应考虑头发色素沉着。
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.