瑞波西汀在中国男性健康志愿者体内的药动学研究

Pharmacokinetics of reboxetine in Chinese male volunteers

目的:考察瑞波西汀在中国男性健康志愿者体内的药动学特点.方法:14例男性健康志愿者单次口服每片含4 mg(R*,R*)-(±)瑞波西汀的甲磺酸瑞波西汀1片,服药前及服药后0.5,1,1.5,2,2.5,3,6,12,24,36,48,60和72 h采取静脉血5 mL,肝素抗凝.给药后各时间点血浆中瑞波西汀的浓度采用高效液相色谱紫外检测法,以210nm波长测定.采用DAS药动学程序求算药动学参数.结果:单次口服甲磺酸瑞波西汀片后,瑞波西汀的血药浓度-时间曲线符合一室模型,主要药动学参数Cmax为(116.91±25.08)ng·mL-1,Tmax为(1.57±0.62)h,t1/2为(12.91±3.32)h,AUC0～72 h为(2 137.27±1 085.93)ng·h·mL-1,AUC0～∞为(2 145.37±1 087.65)ng·h·mL-1,表观分布容积Vd为(36.00±7.16)L,清除率CL/F为(2.12±0.85)L·h-1.受试者服药后的心率和血压有轻度增加,但无心悸的主诉.出现的其他不良反应有恶心、出汗、头晕、排尿不畅、困倦等.这些不良反应均为轻度,无须治疗,可自行缓解.结论:瑞波西汀在中国男性健康志愿者体内的药动学过程与国外文献报道相当.健康志愿者单次口服瑞波西汀4 mg的不良反应轻,耐受性良好.

Objective ：To characterize the pharmacokinetic profile of reboxetine. Methods：14 Chinese male volunteers orally received a single-dose of reboxetine mesilate tablet 4 mg. Five milliliters of blood samples from each volunteers were collected before and 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 36, 48, 60, and 72 h after the oral administration to determine the plasma reboxetine concentrations by high-performance liquid chromatography with ultraviolet detection at 210 nm. The pharmacokinetic parameters of reboxetine were analyzed using DAS program. Results： The plasma reboxetine in the distribution phase showed the one-compartment characteristics after oral administration. The major pharmacokinetic parameters were as following： Cmax（116.91±25.08） ng·mL^-1 , Tmax （1.57±0.62） h, tl/2 （12.91±3.32） h, AUG0-72h （2 137.27±1 085.93） ng·h·mL^-1, AUC0-∞ （2 145.37± 1 087.65） ng·h·mL^-1, Vd（36.00±7.16） L, and CL/F （2.12 ± 0.85） L·h^-1. Heart rate and blood pressure were mildly increased after the oral administration. No palpitation was reported. Other common mild adverse events included nausea, perspiration, dizziness, urinary hesitancy and sleepy. Reboxetine was tolerated well. Conclusion： The pharmacokinetic profile of reboxetine in Chinese healthy volunteers is coincident with the outcomes reported in Western population.