【摘要】 目的研究健康受试者单剂量及多剂量口服福多司坦片后的药代动力学特征。方法36名健康受试者随机分为高、中、低3个剂量组,每组12人,男女各半,分别单剂量口服福多司坦片600,400和200 mg;中剂量组受试者单次口服福多司坦400 mg后,经过1周清洗期,再每日3次,每次400 mg,连续服药5 d。测定血浆中福多司坦的浓度,计算药代动力学参数。结果高、中、低3个单剂量组福多司坦的消除半衰期及体内平均驻留时间相近,AUC0-10 h和Cm ax均与剂量呈线性关系;男性受试者的Tm ax,Cm ax和AUC均小于女性受试者,T1/2均大于女性受试者。统计学结果表明男性与女性间Cm ax和AUC的差异与性别无关,而与体重有关。中剂量组多次给药后的平均稳态血药浓度为(4.1±0.8)μg.mL-1,消除半衰期为(2.5±0.4)h。结论剂量在200~600 mg时,福多司坦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。更多还原

【Abstract】 Aim To study the pharmacokinetics of fudosteine in healthy volunteers after the single and multiple dose administration. Methods Thirty-six volunteers were divided into three groups randomly, each group included six men and six women. In the single dose design, the volunteers received either a single dose of 600 mg, 400 mg or 200 mg fudosteine. After a one-week wash out period, the volunteers of 400 mg group participated in the multiple dose design in which each volunteer received 400 mg fudosteine three times a day for five consecutive days. The plasma concentrations were determined by pre-column derivatization HPLC-FL method and the pharmacokinetic parameters of fudosteine were calculated. Results The obtained pharmacokinetic parameters of fudosteine in single dose of 600 mg, 400 mg and 200 mg groups were as follows: T_1/2 were （2.8±0.5）, （2.7±0.5） and （3.2±0.6） h, respectively. T_max were （0.51±0.22）, （0.59±0.21） and （0.48±0.18） h, respectively. C_max were （16±4）, （11±3） and （6.1±1.5） μg·mL^-1, respectively. The AUC_{0-10 h} and C_max correlated linearly with doses, respectively （r>0.99）. The T_max, C_max and AUC values of fudosteine in healthy male volunteers were smaller than those in female volunteers, and the T_1/2 value was longer than that in female volunteers. The obtained multi-dose pharmacokinetic parameters of fudosteine were as follows: C_ss was （4.1±0.8） μg·mL^-1; DF was 3.0±0.7; T_1/2 was （2.5±0.4） h; T_max was （0.6±0.3） h; C_max was （13.2±1.3） μg·mL^-1. Conclusion The values of pharmacokinetic parameters in healthy volunteers were linear in the range from 200 mg to 600 mg. Statistic analysis results showed that the differences of AUC and C_max between men and women were not resulted from sexual differences, but from the weight differences. There was no significant difference in pharmacokinetic parameters between single dose and multi-dose.更多还原