普瑞巴林缓释片在中国健康男性受试者的人体相对生物利用度及生物等效性研究  

Relative bioavailability and bioequivalence of pregabalin controlled-release tablets in healthy Chinese male volunteers

作　　者：黄洁[1] 阳晓燕[1] 项玉霞[1] 吴淑婷[1] 谭鸿毅[1] 阳国平[1] 裴奇[2] 

机构地区：[1]中南大学湘雅三医院临床药理中心,长沙410013 [2]中南大学湘雅三医院药学部,长沙410013

出　　处：《中国临床药理学杂志》2016年第24期2261-2265,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家国际科技合作专项基金资助项目(2014DFA30900);国家自然科学基金青年基金资助项目(81302851)

摘　　要：目的研究中国健康男性受试者餐后口服两种不同规格的普瑞巴林缓释片与空腹服用普瑞巴林胶囊(乐瑞卡)后的相对生物利用度及生物等效性。方法 24例健康男性受试者按单中心、随机、开放、3周期交叉设计,分别餐后单次给予受试药品T1普瑞巴林缓释片330 mg、餐后单次给予受试药品T2普瑞巴林缓释片330 mg或者空腹2次给予参比药品R普瑞巴林胶囊300 mg,用液质联用法(LC-MS/MS)测定给药后普瑞巴林的血浆浓度,计算主要药代动力学参数,评价两种受试药品相对于参比药品的相对生物利用度及生物等效性。结果服用受试药品T1、T2和参比药品R后,普瑞巴林的主要药代动力学参数为:C_(max)为(4137.92±802.13),(3761.67±516.79),(5792.92±828.34)ng·m L^(-1);tmax为(9.83±2.04),(9.75±2.15),(12.81±0.24)h;AUC_(last)为(64467.78±11266.17),(61434.44±9684.92),(61730.01±6750.94)ng·h·m L^(-1);AUC_(inf)为(65049.66±11405.80),(62019.33±9858.38),(62292.49±6903.74)ng·h·m L^(-1);t1/2为(6.03±0.59),(6.16±0.49),(5.85±0.55)h。受试药品T1与参比药品R的平均相对生物利用度F(AUC_(last))为(104.32±13.05)%,F(AUC_(inf))为(104.31±12.95)%;受试药品T2与参比药品的平均相对生物利用度F(AUC_(last))为(99.58±11.17)%,F(AUC_(inf))为(99.61±11.14)%。受试药品T1、T2与参比药品R的C_(max)和AUC比值的90%置信区间均在80.00%~125.00%。结论餐后口服两种不同规格的普瑞巴林缓释片330 mg和空腹服用普瑞巴林胶囊300 mg后,普瑞巴林的体内暴露量等效,受试药品发挥了很好的缓释特性。Objective To evaluate the relative bioavailability and bioequivalence of two specifications of pregabalin controlled - release tab-lets （test） with food compared to pregabalin capsules （reference） admi- nistered fasted in healthy Chinese male volunteers. Methods This is a single - center, random, open - label, three period cross - over phase I clinical trial. Enrolled 24 healthy male volunteers were given pregabalin controlled- release tablet T1 330 mg （330 mg/tablet x 1, qd）with food, pregabalin controlled - release tablet T2 330 rag（ 165 mg/tablet × 2, qd）with food and pregabalin capsule 300 mg（ 150 mg/capsule ×2, bid） administered fasted. The concentration of pregablin in plasma was measured by LC - MS/MS, the main pharmacokinetic parameters were calculated, and the relative bioavailability and bioequivalence were evaluated. Results The main pharmacokinetic pa- rameters after oral given pregabalin controlled - release tablets T1, T2 and pregabalin capsules were as follows： Cmax were （4137.92 ± 802. 13 ）, （3761.67 ± 516. 79 ） and （5792.92 ± 828.34 ） ng·mL^-1 ;tmax were （9.83±2.04 ）, （9. 75±2.15） and （12.81±0.24） h; AUClast, were （64467.78 ± 11266. 17）, （61434.44 ±9684.92） and （61730.01 ± 6750. 94） ng·h·mL-1; AUCinf were （65049.66 ± 11405.80）, （62019.33 ± 9858.38） and （62292. 49±6903.74）ng·h·mL^-1; t1/2 were （6. 03±0.59）, （6. 16±0. 49） and （5.85±0. 55） h. The relative bioavailability of pregabalin controlled - release tablet T1 were （ 104. 32 ± 13.05 ） % calculated by F（ AUClast ） and （ 104. 31 ± 12.95）% calculated by F（ AUCinf）. The relative bioavailability of pregabalin controlled - release tablet T2 were （99.58 ± 11.17） % calculated by F（AUClast） and （99.61 ± 11.14） % calculated by F（AUCinf）. The 90 % CIs for Cmax and AUC between pregabalin controlled - release tablet T1, T2 and pregabalin capsule were con- tained within 80. 00% - 125.00 %. Conclusion The exposures were e

关 键 词：普瑞巴林 缓释制剂 生物等效 液质联用法 

分 类 号：R976.1[医药卫生—药品]