吡非尼酮在中国健康受试者单剂量及多剂量的药动学研究

何秀玲, 许馨文, 张明,倪晓佳,胡晋卿,王占璋,尚德为,邱畅,温预关

中国药学杂志 ›› 2015, Vol. 50 ›› Issue (13) : 1134-1137.

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中国药学杂志 ›› 2015, Vol. 50 ›› Issue (13) : 1134-1137. DOI: 10.11669/cpj.2015.13.013
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吡非尼酮在中国健康受试者单剂量及多剂量的药动学研究

  • 何秀玲1,3, 许馨文2, 张明1,倪晓佳1,胡晋卿1,王占璋1,尚德为1,邱畅1,温预关1*
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Pharmacokinetics of Pirfenidone after a Single Dose and Multiple-dose Administration in Chinese Healthy Volunteers

  • HE Xiu-ling1,3, XU Xin-wen2, ZHANG Ming1, NI Xiao-jia1, HU Jin-qing1, WANG Zhan-zhang1, SHANG De-wei1, QIU Chang1, WEN Yu-guan1*
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摘要

目的 研究吡非尼酮在中国健康受试者单剂量及多剂量的药动学特征。方法 12名健康受试者随机分成低、中、高3个剂量组(200、400、600 mg)进行单次口服给药,其中400 mg组为多次给药组,连续给药5 d,每天3次,采集第3、4、5天早晨服药前和第5日服药后12 h内血样;采用高效液相色谱-质谱联用测定法测定血浆中吡非尼酮的浓度,并采用DAS程序对试验数据进行处理,计算药动学参数。结果 单次口服200、400、600 mg吡非尼酮的主要药动学参数ρmax分别为(5.00±1.42)、(9.43±2.74)、(14.14±3.36)mg·L-1,tmax分别为(0.57±0.33)、(0.60±0.30)、(0.60±0.38)h,t1/2分别为(2.16±0.77)、(2.15±0.75)、(2.01±0.76)h,AUC(0-∞)分别为(13.87±7.79)、(29.26±12.02)、(45.85±20.25)mg·h·L-1,AUC0-12分别为(13.27±7.08)、(27.92±10.56)、(43.98±18.14)mg·h·L-1。多次给药400 mg后的药动学参数ρmax为(9.46±2.77) mg·L-1,ρmin为(1.14±1.11) mg·L-1,tmax为(0.52±0.34) h,t1/2为(1.93±0.63) h,AUC0-∞为(26.74±13.49) mg·h·L-1,AUC0-12为(25.79 ±12.34) mg·h·L-1,AUCss为(23.53±10.59) mg·h·L-1。结论 吡非尼酮在200~600 mg内ρmax 与AUC与剂量线性关系良好,药动学参数与文献值较为一致。

Abstract

OBJECTIVE To study the pharmacokinetics of pirfenidone in Chinese healthy volunteer after a single dose and multiple-dose administration. METHODS Twelve Chinese healthy volunteers were randomly divided into low, medium and high dose groups(200, 400, 600 mg). The multiple-dose group was administrated with pirfenidione 400 mg three times daily for 5 d. Intensive blood sampling was performed from 12 volunteers within 12 h after the single dosing and the last dose of the multiple dosing. HPLC-MS/MS was used to determine the plasma concentrations of pirfenidone. The pharmacokinetic parameters were calculated by DAS software. RESULTS The main pharmacokinetic parameters of pirfenidone after single-dose administration of 200,400,600 mg qd as follows: ρmax were(5.00±1.42),(9.43±2.74)and(14.14±3.36)mg·L-1;tmax were(0.57±0.33),(0.60 ±0.30)and(0.60±0.38)h;t1/2 were(2.16±0.77),(2.15±0.75)and(2.01±0.76)h; AUC0-∞ were(13.87±7.79),(29.26±12.02)and(45.85±20.25)mg·h·L-1;AUC0-12 were为(13.27±7.08),(27.92±10.56)and(43.98±18.14)mg·h·L-1,respectively. The main pharmacokinetic parameters after 400 mg tid for 5 d were as follows: ρmax was(9.46±2.77)mg·L-1,ρmin was(1.14±1.11)mg·L-1,tmax was(0.52±0.34)h,t1/2 was(1.93±0.63)h,AUC0-∞ was(26.74±13.49)mg·h·L-1,AUC0-12 was (25.79 ±12.34)mg·h·L-1,AUCsswas(23.53±10.59)mg·h·L-1.CONCLUSION The pharmacokinetic parameters of pirfenidone show that ρmax and AUC were linear in the dose range from 200-600 mg and the pharmacokinetic parameters were similar as reference.

关键词

吡非尼酮 / 高效液相色谱-质谱联用 / 药动学

Key words

pirfenidone / HPLC-MS/MS / pharmacokinetics

引用本文

导出引用
何秀玲, 许馨文, 张明,倪晓佳,胡晋卿,王占璋,尚德为,邱畅,温预关. 吡非尼酮在中国健康受试者单剂量及多剂量的药动学研究[J]. 中国药学杂志, 2015, 50(13): 1134-1137 https://doi.org/10.11669/cpj.2015.13.013
HE Xiu-ling, XU Xin-wen, ZHANG Ming, NI Xiao-jia, HU Jin-qing, WANG Zhan-zhang, SHANG De-wei, QIU Chang, WEN Yu-guan. Pharmacokinetics of Pirfenidone after a Single Dose and Multiple-dose Administration in Chinese Healthy Volunteers[J]. Chinese Pharmaceutical Journal, 2015, 50(13): 1134-1137 https://doi.org/10.11669/cpj.2015.13.013
中图分类号: R969.1   

参考文献

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基金

广东省重大科技专项资助项目(2011A080300003);广州市脑科医院广州市医学重点学科建设项目子项目资助项目(GBH2014-ZD07)
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