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目的 比较空腹和高脂餐后顿服胺碘酮的药代动力学变化 ,探讨饮食对胺碘酮药代动力学的影响。方法 8名健康男性志愿者 ,年龄 (2 1 6± 1 2 )岁 ,体重 (6 5 8± 5 6 )kg。志愿者分别在空腹12h和进食标准脂肪早餐 (含黄油 1 5 g/kg体重 )后顿服胺碘酮 80 0mg ,两次服药间隔 12周。高效液相色谱法测定胺碘酮及其代谢产物去乙基胺碘酮浓度 ,计算餐后与空腹服药后药代动力学参数及相对生物利用度。结果 结果显示高脂餐后胺碘酮的血浆浓度较空腹服药明显增高。餐后胺碘酮的峰浓度(Cmax)和血药浓度 时间曲线下面积 (AUC0 t)均较空腹服药显著升高 [Cmax(2 330± 12 14)ng/ml对 (90 3± 35 3)ng/ml;AUC0 t(2 72 6 6± 86 6 7)ng·h·ml-1对 (12 82 5± 5 985 )ng·h·ml-1](P <0 0 1) ;消除半衰期 (t1/ 2 )明显延长 [(2 9 6± 9 8)h对 (17 0± 5 3)h](P <0 0 1) ;达到峰值时间 (Tmax)基本不变 [(4 6±1 2 )h对 (4 6± 1 5 )h]。根据各受试者的AUC计算出高脂餐后服药的相对生物利用度为 2 39%±75 %。结论 高脂餐后服药增加胺碘酮的吸收 ,显著增加胺碘酮的血药浓度 ,同时减慢胺碘酮自体内的消除 ,提示进食高脂餐可能影响药物的疗效。
Objective To compare the pharmacokinetics of amiodarone after fasting and high-fat meals and to investigate the effects of diet on the pharmacokinetics of amiodarone. Methods Eight healthy male volunteers, aged (21 16 ± 12) years and weight (658 ± 56) kg. The volunteers took 80 mg amiodarone twice daily after fasting for 12 hours and standard fat breakfast (including butter 15 g / kg body weight) respectively, for 12 weeks. Determination of amiodarone and its metabolites desethylamine concentration by high performance liquid chromatography, pharmacokinetic parameters and relative bioavailability after meal and fasting medication were calculated. The results showed that high-fat diet amiodarone plasma concentrations were significantly higher than the fasting medication. The postprandial amiodarone peak area (Cmax) and the area under the plasma concentration time curve (AUC0 t) were significantly higher than those on fasting [Cmax (2 330 ± 12 14) ng / ml vs. (90 3 ± 35 3) ng / ml; AUC0 t (7226 ± 8667) ng · h · ml-1 vs (12 82 ± 5 985) ng · h · ml-1] (t1 / 2) was significantly prolonged [(296 ± 98) h vs (17 ± 5 3) h] (P <0.01), and the peak time (Tmax) remained unchanged [(46 ± 1 2) h pair (46 ± 1 5) h]. Based on the AUC of each subject, the relative bioavailability of the high-fat diet was calculated to be 239% ± 75%. Conclusion High-fat meal increases the absorption of amiodarone, which significantly increases the plasma concentration of amiodarone and slows the self-elimination of amiodarone, suggesting that eating high-fat meals may affect the efficacy of drugs.