米屈肼胶囊在中国健康受试者中药代动力学的研究

Pharmacokinetic research of Mildronate Capsule in healthy Chinese subjects

目的研究米屈肼胶囊在健康受试者中单次给药、多次给药的药代动力学规律。方法采用多剂量单序列给药设计方案。12名健康受试者分别按体重由重到轻排序编号,男前女后。统一先服用低剂量250 mg(每粒250 mg×1);经清洗期后服用高剂量1 000 mg(每粒500 mg×2);再经清洗期后服用中剂量500 mg(每粒500 mg×1),并在中剂量下进行连续给药(连续给药6 d,第1~5天每天2次,第6天早上1次,每次500 mg)。结果结果表明在250~1 000 mg剂量范围内,米屈肼呈非线性动力学特征。半衰期随着剂量增加而延长,因此多次服药后在人体内具有明显的蓄积作用。结论本方法适合于米屈肼的人体药代动力学研究。

Objective To study the pharmacokinetics of mildronate capsules in healthy subjects in a single and multiple dose.Methods Using multi-dose of single-sequence for drug design,12 healthy subjects were respectively numbered according to the weight from heavy to light order number,all the female volunteers were behind the male volunteers.All the volunteers were given the low doses of 250 mg （250 mg/pill×1） medicine;After cleaning period all the volunteers were given the high doses of 1 000 mg （500 mg/pill×2） medicine;Again after cleaning period all the volunteers were given the dose 500 mg （500 mg/pill×1） medicine,and then all the volunteers were given the middle-dose of this medicine（oral drug 6 days in a row,oral this medicine twice a day from the first day to the fifth day,oral the medicine once time in the morning of the sixth day,Every time the dose is 500 mg）.Results The pharmacokinetic characteristics of mildronate were nolinear pharmacokinrtics in human body.The t1/2 was prolonged with increasing does,the result of multiple dose indicated the occurrence of accumulation in the multidoses.Conclusion The method developed in this study was suitable for the pharmacokinetic study of mildronate.