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目的:研究中国健康受试者单次和多次口服阿雷地平(AR)肠溶胶囊后阿雷地平(AR)及其主要代谢产物羟基阿雷地平(AR-M1)的药代动力学特征。方法:36名健康受试者,随机分为3组,平行单次口服5,10和20 mg阿雷地平肠溶胶囊的药代动力学研究,10 mg组受试者继续进行多次口服10 mg,qd,连续7 d的药代动力学研究,采用LC-MS/MS法测定血浆中阿雷地平及其主要代谢产物AR-M1的药物浓度,采用DAS 2.1.1软件计算药代动力学参数。结果:单次口服阿雷地平肠溶胶囊5～20 mg后阿雷地平和AR-M1的消除半衰期(t1/2z)分别约为2.0～2.7 h和3.9～5.6 h;达峰浓度(Cmax)随剂量增加呈线性增加,分别为[(2.12±1.14)～(11.34±5.98)μg.L-1]和[(29.41±9.80)～(111.74±24.03)μg.L-1];血药浓度-时间曲线下面积(AUC)也随剂量增加呈线性增加,阿雷地平和AR-M1的AUC0～t分别为[(6.02±2.96)～(30.33±8.88)μg.h.L-1]和[(156.05±32.24)～(776.00±160.47)μg.h.L-1],AUC0～∞分别为[(6.12±2.98)～(30.53±8.89)μg.h.L-1]和[(159.39±33.23)～(785.53±161.92)μg.h.L-1]。多次口服阿雷地平肠溶胶囊10 mg后阿雷地平和AR-M1的t1/2z分别约为2.5和5.5 h,AUC0～t分别为(18.09±5.42)和(604.46±159.66)μg.h.L-1,AUC0～∞分别为(18.25±5.42)和(611.93±162.81)μg.h.L-1。结论:在5～20 mg剂量范围内阿雷地平和AR-M1呈线性药代动力学特征,10 mg多次给药,阿雷地平和AR-M1的Cmax和AUC均较单次给药显著增加,但未见明显蓄积。
OBJECTIVE: To study the pharmacokinetics of Areratriptide (AR) and its major metabolite, hydroxy-Areradipine (AR-M1), after single or multiple oral administration of andrographolide (AR) enteric-coated capsules in healthy Chinese subjects . Methods: Thirty-six healthy volunteers were randomly divided into three groups. The pharmacokinetics of 5, 10 and 20 mg of Aretrianidipine enteric-coated capsules in parallel were given orally. The subjects in the 10 mg group continued oral administration for 10 times mg, qd for 7 consecutive days. Pharmacokinetics of Areradipine and its major metabolite AR-M1 in plasma were determined by LC-MS / MS. The pharmacokinetics was calculated using DAS 2.1.1 software parameter. Results: The elimination half-life (t1 / 2z) of aripiprazole and AR-M1 after oral administration of 5 ~ 20 mg of isodeidipine enteric-coated capsules were 2.0 ~ 2.7 h and 3.9 ~ 5.6 h, respectively. (2.12 ± 1.14) ~ (11.34 ± 5.98) μg.L-1] and [(29.41 ± 9.80) ~ (111.74 ± 24.03) μg.L-1] respectively with the increase of dose.The plasma concentration The area under the curve of time (AUC) also increased linearly with the increase of dose. The AUC0 ~ t of Areratriptin and AR-M1 were respectively (6.02 ± 2.96) ~ (30.33 ± 8.88) μg.hL-1 and (156.05 ± 32.24) ~ (776.00 ± 160.47) μg.hL-1] and AUC0 ~ ∞ were respectively (6.12 ± 2.98) ~ (30.53 ± 8.89) μg.hL-1 and 159.39 ± 33.23 ~ (785.53 ± 161.92) μg.hL-1]. The t1 / 2z of Areratriptin and AR-M1 were about 2.5 and 5.5 h after oral administration of 10 mg of Aretialpine enteric-coated capsules respectively, with AUC0 ~ t of (18.09 ± 5.42) and (604.46 ± 159.66) μg.hL -1 and AUC0 ~ ∞ of (18.25 ± 5.42) and (611.93 ± 162.81) μg.hL-1, respectively. CONCLUSION: Areradipine and AR-M1 have linear pharmacokinetic profiles in the 5-20 mg dose range. Cmax and AUC of Areratripine and AR-M1 were significantly higher than those of single administration Increase, but no significant accumulation.