论文部分内容阅读
本文建立了大鼠的甲状腺机能低下（甲低）和甲状腺机能亢进（甲亢）的动物模型。用HPLC方法测定地西泮的代谢物，以研究甲低和甲亢对SD大鼠单次口服地西泮氧化代谢的影响。甲低组大鼠地西泮的N－去甲基化代谢物去甲地西泮的血药浓度（AUC）升高，消除减慢。说明甲低对地西泮的N－去甲基化影响不大，而主要影响去甲地西泮的C_3－羟化代谢。不同程度甲亢对地西泮氧化代谢的影响有所不同。轻度和中度甲亢组去甲地西泮血药浓度（AUC）低于对照组，消除加快；而重度甲亢组去甲地西泮血药浓度（AUC）略高于对照组，消除减慢。轻、中、重度甲亢大鼠地西泮C_3－羟化代谢物替马西泮血药浓度（AUC）都不同程度地低于对照组，表明仅在重度甲亢对去甲地西泮的C_3－羟化代谢才有抑制性影响，但不同程度甲亢均抑制地西泮的C_3－羟化代谢。
This article established an animal model of hypothyroidism (hypothyroidism) and hyperthyroidism (hyperthyroidism) in rats. The metabolites of diazepam were determined by HPLC to study the effects of hypothyroidism and hyperthyroidism on the single oral oxidizability of diazepam in SD rats. The plasma concentration (AUC) of n-demethylated metabolites of diazepam in diazepam of hypothyroidism rats increased and disappeared. It is concluded that hypothyroidism has little effect on the N-demethylation of diazepam but mainly affects the C_3-hydroxylation of desfopam. Different degrees of hyperthyroidism on the impact of diazepam oxidation metabolism is different. Mild and moderate hyperthyroidism group, the plasma concentration of desferroxen (AUC) was lower than that of the control group, eliminating the accelerated; and severe hyperthyroidism group, the plasma concentration of nidogen (AUC) was slightly higher than the control group, the elimination of slow . The light, moderate and severe hyperthyroidism rat diazepam C_3-hydroxy metabolites of the plasma concentration of alzamide (AUC) were lower than the control group to varying degrees, indicating that only severe hyperthyroidism of n-destriazepan C_3-hydroxylation Metabolism had inhibitory effects, but all levels of hyperthyroidism inhibited C_3-hydroxylation of diazepam.