APPLICATION OF HAIR ANALYSIS TO PREVENT DRUG HAZARDS

这项研究是美国犹他大学人类毒理学中心和日本岐阜市大学医学院药理学系之间的国际合作项目进行了两年。在日本临床毛发分析学会1998年和1999年的年会上，罗林斯教授应邀在T.Uematsu教授的指导下主持了最先进的讲座，并讨论了正在进行的合作研究。此外，日本工作人员还前往美国交流研究信息。在美国，抗菌剂氧氟沙星作为时间标记在头发中的应用在许多不同头发颜色的人类志愿者身上以及在移植了不同颜色头发的人头皮的裸鼠身上都进行了评估。结果，氧氟沙星被证明是头发中的时间标记，与头发的颜色无关。在日本，抗心律失常的氟卡胺，内源性呋喃甲酸，累积…的毛发分析测定肾功能不全患者血清中更多的乌拉酸和毛发蛋白糖基化程度。氟卡胺在患者头发中的累积与头发中的平均浓度成正比，这种药物沿毛干的轴向分布分析揭示了个人过去的药物使用史。虽然肾功能不全患者血清中有FCA积聚，但汗液中HAR的外部污染阻碍了FCA毛发分析对肾功能不全程度的判断。另一方面，头发蛋白质的糖基化程度，即头发中果糖赖氨酸的水解物浓度，随着糖尿病控制的恶化而明显增加，这表明果糖-赖氨酸沿毛干的轴向分布告诉我们个体糖尿病控制几个月的时间分布。总体而言，毛发分析已被证明在追溯个别药物使用方面非常有用，无论头发颜色如何，以及糖尿病疾病状态的时间分布，但不是肾功能不全。较少

This research was conducted for 2 years as international collaboration project between the Center for Human Toxicology, Utah University, USA and the Department of Pharmacology, Gifu University School of Medicine, Japan. At the annual meetings of 1998 and 1999 of the Japanese Society of Clinical Hair Analysis, supervised by Prof. T. Uematsu, Prof. D.E. Rollins was invited to present State-of-Art lectures and to discuss the on-going collaborative research. Also, Japanese staff went to the United States to exchange the research informations. In the United States the usefulness of application of antimicrobial ofloxacin as a time-marker in hair was evaluated both in many human volunteers with different hair colors and in the nude mice transplanted with human scalp with hair of different color. As a result, ofloxacin was shown to act as time-marker in hair irrespective of hair color. In Japan, the hair analyses of antiarrhythmic flecainide, endogeneous furancarboxylic acid (FCA), which accum … More ulates in serum with renal insufficiency, and the degree of hair protein glycation were conducted. Flecainide was shown to accumulate in patient hair in proportion to the mean concentration in hair and the analysis of axial distribution of this drug along the hair shaft revealed the individual past history of drug use. Although FCA accumulates in the serum of patient with renal insufficiency, the external contamination of har through sweat hindered estimating the degree of renal insufficiency by hair analysis of FCA. On the other hand, the degree of glycation of hair protein, which was measured as the concentration of hydrolyzed product of fructose-lysin in hair, clearly increased as the diabetic control was deteriorated, showing that the axial distribution of fructose-lysin along the hair shaft tells us the time-profile of individual diabetic control over several months. As a whole, hair analysis has been shown to be quite useful to trace back individual drug use, irrespective of hair color, and the time-profile of disease state of diabetes mellitus, but not of renal insufficiency. Less