高脂饮食对阿雷地平及其活性代谢产物人体药动学特征的影响

Effect of high-fat food intake on pharmacokinetics of aranidipine and its active metabolite in healthy Chinese volunteers

目的评价高脂餐对阿雷地平及其活性代谢产物羟基阿雷地平在健康中国人体内药动学的影响。方法10名健康男性受试者空腹口服阿雷地平10 mg,经过1 wk清洗期后,受试者高脂餐后口服阿雷地平10 mg。采用液相色谱-串联质谱联用法测定血浆中阿雷地平及其活性代谢产物羟基阿雷地平的浓度。结果空腹和高脂餐后口服阿雷地平,阿雷地平的c_(max)分别为(2.4±s0.8)和(4.4±2.9)μg·L^(-1),羟基阿雷地平的c_(max)分别为(41±10)和(51±19)μg·L^(-1);空腹和高脂餐后阿雷地平和羟基阿雷地平的c_(max)无显著差异。空腹和高脂餐后口服阿雷地平,阿雷地平的AUC_(0～36)分别为(10.3±2.3)和(15±7)μg·h·L^(-1),羟基阿雷地平的AUC_(0～36)分别为(305±108)和(389±129)μg·h·L^(-1);阿雷地平的t_(max)分别为(4.4±1.0)和(9±6)h,羟基阿雷地平的f_(max)分别为(5.0±1.6)和(11±7)h;空腹和高脂餐后阿雷地平和羟基阿雷地平的AUC_(0～36)和t_(max)均存在显著差异,AUC显著增加,t_(max)显著延长。结论高脂餐后,阿雷地平的吸收出现延迟现象,吸收程度有所增加;羟基阿雷地平的体内生成延迟,但生成的量增加。

AIM To investigate the effects and its active metabolite, hydroxyl-aranidipine, of food intake on the pharmacokinetic profiles of aranidipine in healthy Chinese male volunteers. METHODS Ten male volunteers aged from 18 to 35 were orally administrated with aranidipine tablet 10 mg. After a washout period of a week, volunteers were orally administrated with aranidipine tablet 10 mg after high-fat meal. Plasma concentrations of aranidipine and hydroxyl-aranidipine were determined by HPLC-MS/MS. RESULTS Under fasting and fed conditions, cmax of aranidipine were （2.4 ±s 0.8） and （4.4±2.9） μg·L-1 respectively, cmax of hydroxyl-aranidipine were （41 ± 10） and （51 ±19） μg·L-1, respectively. There was no significant difference in cmax for both aranidipine and hydroxyl-aranidipine. Under fasting and fed conditions, A UC0-36 of aranidipine were （10.3 ±2.3） and （15±7） μg·L-1, AUCo_36ofhydroxyl-aranidipinewere （305 ± 108） and （389 ± 129）μg·L-1. tmax of aranidipine were （4.4 ±1.0） and （9 ± 6） h, tmax of hydroxyl-aranidipine were （5.0 ＋ 1.6） and （ 11 ± 7） h. There was significant increasing in A UC0-36 and tmax for both aranidipine and hydroxyl-aranidipine under fed condition. CONCLUSION Aranidipine shows delay in absorption and increase in absorption level after high-fat meal. The generation of hydroxyl-aranidipine also delays, but the amount of hydroxyl-aranidipine increases.