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观察了给大鼠单剂及多剂乙胺碘呋酮(简称胺碘酮)后血清、心肌及脂肪组织药浓度的动态变化,并比较了单剂和多剂给药条件下血浆、心肌药浓度和抗心律失常作用的关系。口服单剂50mg/kg后2～8小时血清及心肌药浓度相对平稳,后者约为前者的20倍。脂肪药浓度在16小时内持续上升。大鼠每天口服50mg/kg,服药3～28天期间心肌与血清药浓度比值平稳在14～16范围内,而脂肪与血清药浓度比值持续上升,给药第28天达106。多剂服药期间还看到血清反T_3持续缓慢上升,其变化大致与血清或心肌胺碘酮的变化平行。进行了5批抗心律失常试验,其中3批用结扎冠状动脉模型,2批用去甲肾上腺素模型。发现口服多剂(20mg/kg/d×5)后心肌药浓度虽较静脉注射单剂(20mg/kg)者低,但其抗心律失常作用则较好。对这种现象的机制进行了讨论。
The dynamic changes of serum, myocardial and adipose tissue concentrations in rats after single and multi-dose amiodarone (amiodarone) administration were observed. The effects of single and multi-dose administration of plasma and cardiomyocyte drug Relationship between concentration and antiarrhythmic effect. After oral administration of 50mg / kg 2 to 8 hours serum and myocardial drug concentration is relatively stable, which is about 20 times the former. Fat concentration continued to rise within 16 hours. Oral administration of 50mg / kg rat daily, medication for 3 to 28 days, myocardial and serum drug concentration ratio remained stable in the range of 14 to 16, and fat and serum drug concentration ratio continued to rise, the day of administration of up to 106. Multi-dose medication period also saw continued anti-T_3 continued to rise slowly, the change is roughly parallel with changes in serum or cardiac amiodarone. Five batches of antiarrhythmic tests were performed, three of which were used to ligate a coronary artery model and two to use a norepinephrine model. It was found that the cardiac drug concentration after oral administration of 20 mg / kg / d × 5 was lower than that of single intravenous injection (20 mg / kg), but its antiarrhythmic effect was better. The mechanism of this phenomenon is discussed.