Nakahara Y, Kikura R
National Institute of Health Sciences, Tokyo, Japan.
Arch Toxicol. 1994;68(1):54-9.
We studied the incorporation rates of cocaine and its major metabolites, benzoylecgonine (BE) and ecgonine methylester (EME), into hair from blood. It was demonstrated in our previous report (Nakahara et al. 1992a) that the incorporation rate of cocaine from blood into hair was much higher than those of BE and EME following administration of cocaine. In this study, the incorporation rates of these drugs into rat hair were investigated following independent administration of BE and EME at 10 mg/kg per day for 5 days, and co-administration of cocaine, BE-d3 and EME-d3 at 3, 0.5 and 0.5 mg/kg per day for 10 days. When BE and EME were administered to rats independently, levels of both these drugs were hardly detectable or quite low in hair, though their AUCs in plasma were very high. On co-administration of cocaine, BE-d3 and EME-d3, the deuterium labeled metabolites in hair were negligibly lower in comparison with the unlabeled ones and in particular the concentration of BE in rat hair was significantly higher than that of BE-d3 although the AUC of BE-d3 was higher than that of BE. It was concluded that the incorporation rates of BE and EME into hair were very low in comparison with that of cocaine and most of the BE detected in hair would be a hydrolytic product derived from cocaine in hair matrix after incorporation.
我们研究了可卡因及其主要代谢物苯甲酰芽子碱（BE）和芽子碱甲酯（EME）从血液进入毛发的掺入率。我们之前的报告（Nakahara等人，1992a）表明，给予可卡因后，可卡因从血液进入毛发的掺入率远高于BE和EME。在本研究中，分别以每天10mg/kg的剂量独立给予BE和EME，持续5天，以及以每天3mg/kg、0.5mg/kg和0.5mg/kg的剂量共同给予可卡因、BE-d3和EME-d3，持续10天，之后研究这些药物进入大鼠毛发的掺入率。当单独给大鼠施用BE和EME时，尽管它们在血浆中的曲线下面积（AUC）非常高，但在毛发中几乎检测不到这两种药物的水平或水平非常低。在共同施用可卡因、BE-d3和EME-d3时，毛发中氘标记的代谢物与未标记的代谢物相比可忽略不计地较低，特别是大鼠毛发中BE的浓度显著高于BE-d3，尽管BE-d3的AUC高于BE。得出的结论是，与可卡因相比，BE和EME进入毛发的掺入率非常低，并且毛发中检测到的大部分BE将是掺入后毛发基质中可卡因衍生的水解产物。
