食物对吡非尼酮胶囊人体药动学的影响  

Effect of Food on the Pharmacokinetics of Pirfenidone Capsules in Healthy Volunteers

作　　者：李忠芳 吴健鸿[2] 陈汇[2] 罗楹 曾繁典[2] 师少军[4] Li Zhongfang;Wu Jianhong;Chen Hui;Luo Ying;Zeng Fandian;Shi Shaojun(Department of Obstetrics ＆ Gynecology,Union Hospital,Tongii Medical College,Huazhong University of Science and Technology,Wuhan 430022,China;Institute of Clini-cal Pharmacology,Tongii Medical College,Huazhong University of Science and Technology;Shanghai Genomics Inc.;Depart-ment of Pharmacy,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology)

机构地区：[1]华中科技大学同济医学院附属协和医院妇产科,武汉430022 [2]华中科技大学同济医学院临床药理研究所 [3]上海睿星基因技术有限公司 [4]华中科技大学同济医学院附属协和医院药剂科

出　　处：《中国药师》2018年第10期1731-1734,共4页China Pharmacist

摘　　要：目的:比较健康受试者空腹、餐后单剂量口服吡非尼酮胶囊的药动学。方法:健康受试者12名(男女各半),随机交叉空腹、餐后单剂量口服吡非尼酮胶囊400 mg,HPLC法测定其血药浓度,DAS v2. 0软件计算药动学参数。结果:空腹和餐后单剂量口服吡非尼酮胶囊的药时曲线均符合一级吸收的一室模型。空腹和餐后服药的药动学参数:t_(1/2)分别为(2. 16±0. 47),(2. 05±0. 42) h; t_(max)分别为(0. 69±0. 16),(1. 46±0. 40) h; C_(max)分别为(12. 95±1. 79),(9. 16±2. 87) mg·L^(-1); AUC_(0-12)分别为(44. 97±15. 06),(36. 19±14. 44) mg·h·L^(-1); AUC_(0-∞)"分别为(46. 55±16. 79),(37. 41±15. 43) mg·h·L^(-1)。与空腹给药组比较,餐后服用吡非尼酮胶囊可以显著延长药物t_(max)(P <0. 001),降低其C_(max)(P <0. 001)和AUC(P <0. 01)。结论:进食对吡非尼酮胶囊药动学具有显著影响,可减慢其吸收速率,并降低其吸收程度,与患者耐受性更好相关。Objective： To compare the pharmacokinetics and bioavailability of pirfenidone in the fasted and fed states in healthy volunteers. Methods： An open-label,randomized crossover study was conducted in 12 healthy subjects. Food effects were examined by comparing pharmacokinetic data of pirfenidone after administration of a single oral 400 mg dose under fasted or fed conditions. Plasma pirfenidone concentration was determined by an HPLC method and its pharmacokinetic parameters were calculated with DAS v2. 0 software. Results： Under fasted and fed conditions,the concentration-time profiles of pirfenidone were fitted a one-compartment model and the pharmacokinetic parameters were as follows： t1/2 were（ 2. 16 ± 0. 47） and（ 2. 05 ± 0. 42） h; tmax were（ 0. 69 ± 0. 16） and（ 1. 46 ± 0. 40） h; Cmaxwere（ 12. 95 ± 1. 79） and（ 9. 16 ± 2. 87） mg·L^-1; AUC0-∞ were（ 44. 97 ± 15. 06） and（ 36. 19 ± 14.44） mg·h·L^-1; AUC0-∞were（ 46. 55 ± 16. 79） and（ 37. 41 ± 15. 43） mg·h·L^-1,respectively. When compared with that of the fasted group,tmaxwas significantly increased（ P〈0. 001） while Cmax and AUC were remarkedly decreased in the fed group（ P〈0. 001 and P〈0. 01,respectively）. Conclusion： Concomitant food intake significantly influences the pharmacokinetics and bioavailability of pirfenidone as indicated by reducing its extent and rate of absorption,which is associated with better tolerability.

关 键 词：吡非尼酮 食物 药动学 生物利用度 

分 类 号：R969.1[医药卫生—药理学]