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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 healthy Chinese. Methods: The analytical column of Inspire-C 18 (150 mm × 4.6 min, 5 μm, Dikma) was used. The mobile phase consisted of methanol and water containing 0.02% phosphoric acid (59:41). The detection wavelength was 310 nm and the flow rate was 1 ml · Min ~ (-1). The plasma samples were directly injected after the protein was precipitated by 10% perchloric acid solution. Thirty healthy subjects were randomly divided into three groups: low, medium and high doses of 10, each with a half male and a female. Each group received 200, 400 and 600 mg of pirfenidone orally. The plasma concentrations of pirfenidone The pharmacokinetic parameters were calculated using WinNonLin 6.2. Results: The lowest limit of quantification of pirfenidone in human plasma was 0.2 μg · ml -1, with a good linearity in the range of 0.2 ~ 25 μg · ml -1. The mean intra-and inter-assay RSD Less than 15%. The main pharmacokinetic parameters were as follows: C max 6.08 ± 6.08, (11.97 ± 1.34) and (15.71 ± 1.74) μg · ml -1; t max were 0.63 ± 0.13, (0.63 ± 0.23) and (0.58 ± 0.19) h, respectively; t 1/2 was 2.02 ± 0.47, 2.15 ± 0.50 and 2.59 ± 0.56 h respectively; AUC 0-t was 14.79 ± 3.04), (29.54 ± 8.50) and (47.02 ± 5.85) μg · h · ml -1, respectively. The AUC 0 -∞ were (15.77 ± 3.21), (30.67 ± 9.15) and (50.06 ± 6.07) ) μg · h · ml -1. CONCLUSION: AUC 0-0, AUC 0-0 and C max of pirfenidone in three dose groups (200-600 mg) are dose-dependently linear.