摘要
目的 研究健康受试者单剂和连续口服胺碘酮后原形药物和活性代谢物去乙基胺碘酮的药代动力学特点及相互关系。方法 36例健康男性受试者分两组。单剂量组 2 0例 ,服药 80 0mg/次 ;多剂量组 1 6例 ,服药 60 0～ 80 0mg/d ,连续服药至停药标准。采用反相HPLC方法同时测定受试者胺碘酮和去乙基胺碘酮血药浓度 ,并计算药代动力学参数。主要药代动力学参数比较采用方差分析。结果 (1 )单剂量组 :胺碘酮和去乙基胺碘酮的达峰时间 (Tmax)分别为 (5 2± 1 5)h和 (8 6± 3 2 )h ,峰浓度 (Cmax)分别为 (0 764± 0 383)mg/L和 (0 1 2 6± 0 0 71 )mg/L ,0至 48h取样的血药浓度 时间曲线下面积 (AUC0 4 8)分别为 (1 0 593± 4 977)mg·h·L- 1 和 (3 936± 1 2 88)mg·h·L- 1 ;(2 )多剂量组 :胺碘酮和去乙基胺碘酮间Tmax和末端消除速率常数 (Ke)差异无显著性 (P >0 0 5) ;其余药代动力学参数Cmax、Tmax、AUC0 4 8等两者之间差异有显著性 (P <0 0 1 )。口服两种负荷剂量后 ,代谢物的各药代动力学参数两组间差异无显著性。结论 无论是单剂或短期连续口服胺碘酮 ,其原形药物、去乙基胺碘酮均存在滞后作用 。
Objective To study the pharmacokinetic parameters of amiodarone (Am) and desethylamiodarone (DEA) and the relationship between Am and DEA in healthy volunteers after a single oral dose and multiple doses Methods A single dose of Am (800 mg) was given to 20 healthy male volunteers, and multiple doses of Am (600-800 mg/d) were given to 16 healthy male volunteers The concentrations of Am and DEA in plasma were measured by HPLC The pharmacokinetic parameters were calculated The analysis of variance was applied for main pharmacokinetic parameters Results (1)The single dosage group: T max of Am and DEA were (5 2±1 5)h and (8 6±3 2)h; C max were (0 764±0 383) mg/L and (0 126±0 071) mg/L; AUC 0 48 were (10 593±4 977) mg·h·L -1 and (3 936±1 288) mg·h·L -1 , respectively; t 1/2 of Am was (16 7±5 4 )h; Ke of Am was (0 045±0 013) h -1 (2) The multiple dosage group: no significant difference of T max and Ke between Am and DEA was found ( P >0 05) There were significant differences of the other pharmacokinetic parameters between Am and DEA( P <0 01) No significant difference in pharmacokinetic parameters of DEA was found between 800 mg and 600 mg dosage ( P >0 05) Conclusions DEA is delayed in both single dose group and multiple dose group The cumulated effects of amiodarone and its active metabolite should be considered in clinical use
出处
《中华心血管病杂志》
CAS
CSCD
北大核心
2003年第1期29-32,共4页
Chinese Journal of Cardiology
