健康人连续口服不同剂量胺碘酮的血药浓度的临床研究

目的　比较中国健康受试者连续口服胺碘酮不同剂量后,各种药代动力学参数的特点。方法　16名健康男性受试者随机分为两组,第一组 (A组 )连续口服胺碘酮 800mg·d-1;第二组(B组 )连续口服胺碘酮 200mg·d-1。采用HPLC法测定血浆中的胺碘酮及其代谢物去乙基胺碘酮浓度。结果　A、B两组的达峰浓度Cmax分别为 ( 1 17±0 38 )和(0 84±0 33)mg·L-1,达峰时间Tmax分别为(4 0±2 0)和(5 1±1 4)h,终末消除半衰期 (T1 /2 )分别为 ( 410 5±137 1)和(345 9±237 0)h,组间比较均无差异;A组、B组起作用浓度分别为 ( 0 93±0 28 )和 ( 0 57±0 25 ) mg·L-1,差异有统计学意义;A组、B组发生药物反应的时间及累积剂量基本一致;发生药物反应的浓度A组 ( 0 71 ~1 34)mg·L-1,B组 ( 0 29 ~1 11 )mg·L-1。结论　在一定时间内,随口服胺碘酮剂量增加,血药浓度相应增加,提示在临床用药中如在开始用药时通过给与较大剂量的负荷量,可能获得更快的起效作用。

The concentrations of amiodarone of multiple-dose 800 mg·d-1 and 600 mg·d-1 amiodarone in healthy subjects

Aim To study the pharmacokinetics of amioda rone in healthy subjects receiving 800 mg·d -1 (Group A) and 600 mg·d -1 (Group B) regimens.Methods 16 subjects were divided into t wo groups randomly, which were given amiodarone 800 mg·d -1 and 600 mg·d -1 respectively. The plasma concentrations of amiodarone and its metabolit e desethyl-amiodarone were determined by HPLC.Results The phar macokinetic parameters of 800 mg·d -1 and 600 mg·d multiple-dose groups were: C max(1.17±0.38) and (0.84±0.33) mg·L -1; T max(4 .0±2.0) and (5.1±1.4) h; T 1/2(410.5±137.1) and (345.9±237 .0) h.The initial effective concentrations of the two groups were (0.93±0.28 ) mg·L -1 and (0.57±0.25) mg·L -1 respectively (P<0.05), gre at individual variations were found in both groups (Group A: 0.71～1.34 mg·L -1; Group B: 0.29～1.11 mg·L -1). Conclusion The concentrations of amiodarone increased along with the dose increase in certain d uration indicating that it might take shorter time to reach therapeutic effect i f high loading doses were administered.