盐酸舍曲林胶囊的生物等效性评价

Pharmacokinetics and relative bioavailability of sertraline hydrochloride capsules in healthy volunteers

目的研究盐酸舍曲林胶囊的人体相对生物利用度和生物等效性。方法 健康志愿者18名,随机双交叉单剂量po盐 酸舍曲林胶囊(受试制剂)和盐酸舍曲林片(参比制剂),剂量均为100 mg,间隔为2周。分别于服药后120 h内多点抽取静脉 血;用高效液相色谱法测定血浆中舍曲林的质量浓度。用3P97药动学程序计算相对生物利用度并评价两者的生物等效性。 AUC0-120,AUC0-inf和ρmax经方差分析和双单侧t检验,tmax进行秩和检验。结果 单剂量po受试制剂和参比制剂后血浆中的 舍曲林的ρmax分别为(42．1±8．4)和(41．2±6．5)μg·L-1;tmax分别为(5．1±1．0)和(4．6±1．0)h;AUC0-120分别为(1 549．6± 315．0)和(1 474．0±299．562)μg·h·L-1;AUC0-inf分别为(1 710．0±322．6)和(1 639．6±314．5)μg·h·L-1。ρmax的90％可信区间为 95．6％～107．5％,AUC0-120的90％可信区间为96．2％～114．6％,AUC0-inf的90％可信区间为96．4％-112．9％。结论 两者的 人体相对生物利用度为(107．2±22．5)％,两者具有生物学等效性。

OBJECTIVE To study the relative bioavailability and bioequivalenee of Sertraline Hydroc, hloride capsules and tablets in healthy volunteers. METHODS A single oral dose of 100 mg capsules and tablets was given to 18 healthy volunteers in a randomized crossover study. The concentrations of Sertraline in plasma were determined by HPLC. The pharmacokinetic parameters were calculated and the bioavailability and bioequivalence of two formulations were evaluated by 3P97 program. RESULTS After a single dose, the pharmacokinetic parameters for Sertraline capsules and reference formulation were as follows： ρmax（42.1± 8.4） and （41.2±6.5） μg·L^-1 ; tmax（5.1±1.0） and （4.6±1.0） h; AUC0-120（1 549.6±315.0） and （1 474.0±299.6） μg·h·L^-1; AUC0-inf（1 710.0±322.6） and （1 639.6±314.5） μg·h·L^-1, respectively. The 90 % confidential interval of ρmax of capsule was 95.6 % - 107.5 %, The 90 % confidential interval of AUC0-120 and AUC0-inf of capsule were 96.2% - 114.6% and 96.4% - 112.9% ,respectively. CONCLUSION The relative bioavailability of capsules and tablets is （ 107.2 ± 22.5） % ; The results of the statistic analysis show that the test and reference formulations are bioequivalence.