吡非尼酮片在中国健康人体的药动学研究

Study on Pharmacokinetics of Pirfenidone Tablets in Chinese Healthy Volunteers

目的:研究吡非尼酮片在中国健康人体的药动学特征。方法:采用Inspire-C_(18)(150 mm×4.6 min,5μm,Dikma)分析柱,甲醇-水含0.2%的磷酸(59:41)为流动相,检测波长为310 nm,流速为1 ml·min^(-1);血浆样品经10%高氯酸溶液沉淀蛋白后直接进样。30名健康受试者随机分为低、中、高3个剂量组,每组10人(男女各半),分别单次口服吡非尼酮片200,400,600 mg,采用HPLC测定血浆中吡非尼酮的浓度并采用WinNonLin 6.2计算药动学参数。结果:人血浆中吡非尼酮的最低定量限为0.2μg·ml^(-1),在0.2～25μg·ml^(-1)范围内线性关系良好,批内及批间精密度RSD均小于15%。主要药动学参数:C_(max)分别为(6.08±6.08)、(11.97±1.34)和(15.71±1.74)μg·ml^(-1);t_(max)分别为(0.63±0.13)、(0.63±0.23)和(0.58±0.19)h;t_(1/2)分别为(2.02±0.47)、(2.15±0.50)和(2.59±0.56)h;AUC_(0-t)分别为(14.79±3.04)、(29.54±8.50)和(47.02±5.85)μg·h·ml^(-1);AUC_(0-∞)分别为(15.77±3.21)、(30.67±9.15)和(50.06±6.07)μg·h·ml^(-1)。结论:3个剂量组(200～600 mg)中吡非尼酮在人体内的AUC_(0-t),AUC_(0-∞)和C_(max)均与剂量呈线性关系。

Objective：To study the pharmacokinetics of pirfenidone tablets in Chinese healthy volunteers.Method：The plasma samples were analyzed on an Inspire-C_（18）（150 mm×4.6 mm,5μm,Dikma） column with methanol-water（0.2%phosphoric acid） （59：41） as the mobile phase.The flow rate was 1 ml ？ min^（-1） and the detection wavelength was 310 nm.The samples were denatured by 10%perchloric acid.Thirty healthy volunteers were randomly divided into three groups with 10 volunteers in each group（5 males and 5 females）.The three groups received pirfenidone tablets with a single dose of 200,400 and 600 mg,respectively.The concentrations of pirfenidone in human plasma at different times were determined by HPLC and the pharmacokinetic parameters were calculated by WinNonLin 6.2 software.Result：The limit of quantitation（LOQ） of pirfenidone was 0.2μg ？ ml^（-1）.The calibration curve was linear over the range of 0.2-25μg ？ ml^（-1）.The intra- and inter-day RSDs were less than 15%.The pharmacokinetic parameters were as follows;C_（max） of（6.08±6.08）,（11.97±1.34）and（15.71±1.74）μg ？ ml^（-1）,t_（max） of（0.63±0.13）,（0.63±0.23）and（0.58±0.19）h,t_（1/2）of（2.02±0.47）,（2.15±0.50） and（2.59±0.56）h,AUC_（0-t） of（14.79±3.04）,（29.54±8.50）and（47.02±5.85）μg·h·ml^（-1）,and AUC_（0-∞） of（15.77±3.21）,（30.67±9.15） and（50.06±6.07）μg ？ h ？ ml^（-1）.Conclusion：The values of AUC_（0-t）,AUC_（0-∞） and C_（max） are linear within the dose range of 200-600 mg.