Gonska B D, Bethge K P, Wagner H, Bosse K, Köbberling J, Quentin C D, Kreuzer H
Klin Wochenschr. 1986 Mar 3;64(5):219-26. doi: 10.1007/BF01711651.
Thirty-eight patients with refractory supraventricular and ventricular tachyarrhythmias were administered a mean oral dosage of 400 mg amiodarone daily (200-600 mg). A high-pressure liquid chromatography method was used to measure serum concentrations of amiodarone and its metabolite desethylamiodarone after one week, one month, three months, and then at 6-month intervals. In 24 patients subcutaneous fatty tissue concentrations were also measured. The mean follow-up was 9 months (4 days to 29 months). A linear correlation was found between amiodarone and its metabolite in serum (r = 0.56, p less than 0.001) as well as in subcutaneous fatty tissue (r = 0.67, p less than 0.001). While serum concentrations were dose dependent, tissue concentrations accumulated during chronic therapy (p less than 0.01, both). Clinical efficacy was achieved in 84% of the patients. No statistically significant difference was found between responders and non-responders as regards serum and subcutaneous fatty tissue concentrations. Side effects of amiodarone occurred in 63%. The incidence of adverse effects was related to significantly higher serum and subcutaneous fatty tissue concentrations of amiodarone and its metabolite (p less than 0.001, both). Thus, although the determination of serum and subcutaneous fatty tissue concentrations does not seem to be helpful for assessing clinical efficacy of this antiarrhythmic drug, these values may predict the occurrence of adverse effects.
38例难治性室上性和室性快速性心律失常患者每日口服胺碘酮的平均剂量为400毫克(200 - 600毫克)。采用高压液相色谱法在1周、1个月、3个月后以及随后每6个月测量一次血清中胺碘酮及其代谢产物去乙基胺碘酮的浓度。对24例患者还测量了皮下脂肪组织中的浓度。平均随访时间为9个月(4天至29个月)。发现胺碘酮与其代谢产物在血清中的浓度呈线性相关(r = 0.56,p < 0.001),在皮下脂肪组织中也呈线性相关(r = 0.67,p < 0.001)。虽然血清浓度呈剂量依赖性,但在长期治疗过程中组织浓度会累积(两者p均< 0.01)。84%的患者取得了临床疗效。在反应者和无反应者之间,血清和皮下脂肪组织浓度方面未发现统计学上的显著差异。63%的患者出现了胺碘酮的副作用。不良反应的发生率与胺碘酮及其代谢产物在血清和皮下脂肪组织中的浓度显著升高有关(两者p均< 0.001)。因此,虽然测定血清和皮下脂肪组织浓度似乎无助于评估这种抗心律失常药物的临床疗效,但这些值可能预测不良反应的发生。