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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1. Institution of National Drug Clinical Trials of Guangzhou Brain Hospital,Guangzhou Medical University, Guangzhou 510370, China; 2. Zhuhai Ebang Pharmaceutical CO.,LTD., Zhuhai 519041, China; 3. Department of Pharmacy,People′s Hospital of Jiangmen Xinhui, Jiangmen 529100, China
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.
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
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