甲胺及其代谢产物甲醛在动物体内的药代动力学  

Pharmacokinetics of methylamine and its metabolite formaldehyde in animals

作　　者：罗红军[1] 李慧[1] 罗文鸿[1] 

机构地区：[1]汕头大学医学院中心实验室,广东汕头515031

出　　处：《中国药理学与毒理学杂志》2006年第2期120-124,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助项目(30271139);广东省自然科学基金资助项目(021224);中国教育部资助项目(2003/335)~~

摘　　要：目的 进一步了解血浆氨基脲敏感型胺氧化酶（SSAO）活性与内源性甲醛的生理学与病理学意义。方法 采用高效液相色谱法测定小鼠、大鼠和兔血浆中SSAO活性和静脉给予甲胺后甲胺及其代谢产物甲醛浓度。结果 小鼠、大鼠和兔血浆中SSAO活性分别为（4．1±1．0），（2．0±0．3）和（325．8±3．9）μmol·h^-1·L^-1。3种动物单次iv甲胺后，甲胺的分布和代谢迅速。小鼠单次iv 4．2mg·kg^-1甲胺后甲醛浓度在代谢初期缓慢上升，在20-40min达峰后缓慢消除。而大鼠单次iv 4．2mg·kg^-1甲胺后血浆甲醛浓度无明显改变。兔单次iv 2．3，9．6和36．8mg·kg^-1甲胺后，甲胺AUC与剂量不成比例，Cl随剂量增加明显减少，呈非线性动力学特征。甲醛在兔体内消除较快，甲醛AUC与甲胺剂量的比值和全身清除率Cl无明显差异，但ke随给予甲胺剂量的增大而减少，t1／2显著延长。结论 甲胺在3种动物间代谢情况相似，其代谢产物甲醛则明显不同。甲胺给予剂量的不同可能导致甲胺代谢动力学的改变，进而可能影响甲醛的代谢。AIM For further understanding the physiological and pathological significance of plasma semicarbazide-sensitive amine oxidase （SSAO） activity and endogenous formaldehyde. METHODS Plasma SSAO activity, methylamine hydrochloride （MA） and its metabolite formaldehyde （FA） concentrations were determined by HPLC after iv MA to mice, rats and rabbits. REULTS Plasma SSAO activities of mice, rats and rabbits were（4.1 ± 1.0）, （2.0 ±0.3） and （326 ±24）μmol·h^-1·L^-1, respectively. MA was distributed and cleared quickly in mice, rats and rabbits. After iv 4.2mg·kg^-1 MA to mice, FA increased and reached maximum concentration between 20 - 40 min, and then eliminated slowly. However, FA did not changed obviously compared with its baseline in rats after iv 4.2 mg·kg^-1 MA. In rabbits, Cl decreased with the increase in MA dosage and AUC was not in proportion to the dosage after iv 2.3,9.6 and 36.8 mg·kg^-1 MA, showing the characteristics of nonlinear kinetics. FA was distributed rapidly,AUC was in proportion to MA dosage and Cl did not change obviously. However, ke decreased and t1/2 extended significantly with the increase in MA dosage. CONCLUSION The pharmacokinetics of MA was similar, but its metabolite FA was different in mice, rats and rabbits. The difference of MA dosage administrated may change the pharmacokinetics of MA and have an impact on FA＇s metabolism.

关 键 词：氨基脲敏感型胺氧化酶 甲胺 甲醛 药代动力学 

分 类 号：R96[医药卫生—药理学]