四烯甲萘醌软胶囊在健康中国志愿者体内的药动学研究

Study on the Pharmacokinetics of Menatetrenone Soft Capsule in Healthy Chinese Volunteers

目的：建立人血浆中四烯甲萘醌的LC-APCI-MS测定方法,研究四烯甲萘醌软胶囊在健康中国人体内的单、多剂量药动学特征。方法：24名健康受试者随机分为I、II两组,每组12人,男女各半,进行单剂量口服四烯甲萘醌软胶囊15 mg、30 mg、45 mg的低、中、高三个剂量的单次给药药动学试验,以及每日3次,每次15 mg的多次给药药动学试验。以LC-APCI-MS法测定血浆中口服四烯甲萘醌的浓度,计算药代动力学参数。结果：高、中、低3个单剂量组口服四烯甲萘醌的消除半衰期及体内平均驻留时间相近,AUC0-10、Cmax均与剂量呈线性关系;15 mg剂量组多次给药后的平均稳态血药浓度为（87.3±23.4）ng·mL^-1,稳态血药浓度波动系数为1.1±0.5。结论：在15－45 mg剂量范围内口服四烯甲萘醌在健康受试者体内呈线性药代动力学特征,多剂量给药与单剂量给药的药代动力学参数基本一致。

Objective： To establish an LC-APCI-MS method for the determination of menatetrenone in human plasma and study the pharmacokinetics of menatetrenone soft capsule in healthy Chinese volunteers after single and multiple dose administration.Methods： Twenty-four volunteers were divided into two groups randomly.Each group included six men and six women.In the single dose design,the volunteers received a single dose of 15 mg,30 mg and 45 mg menatetrenone.In the multiple dose design,the volunteers received 15 mg menatetrenone three times a day for six consecutive days.The plasma concentrations were determined by LC-APCI-MS method and the pharmacokinetic parameters of menatetrenone were calculated.Results： The obtained pharmacokinetic parameters t1/2 and MRT of menatetrenone in three single dose tests of 15 mg,30 mg and 45 mg were similar.The AUC0-24 and Cmax correlated linearly with doses,respectively（r0.99）.The obtained multi-dose pharmacokinetic parameters of menatetrenone were as follows： the Css was（87.3±23.4 ng·mL^-1.the DF was 1.1±0.5.Conclusion： The pharmacokinetics of menatetrenone in healthy Chinese volunteers was linear in the dose range of 15 mg-45 mg.There was no significant difference in pharmacokinetic parameters between the single dose and multi-dose administration.