中国健康志愿者单剂口服甲磺酸加替沙星片的药代动力学研究

A single dose pharmacokinetics of gatifloxacin mehanesulfanae tablets in Chinese healthy volunteers

目的研究中国健康成年志愿者单剂口服甲磺酸加替沙星片的药代动力学。方法按GCP指导原则设计试验方案,选择9名健康受试者分别依次单剂口服200、400、600mg三个剂量的甲磺酸加替沙星片后,应用HPLC测定血药浓度,采用3P97软件进行数据处理,求出药代动力学参数。结果受试者分别给药后,药-时曲线符合二房室模型,主要药代动力学参数Cmax分别为(2.028±0.362)mg/L、(3.749±0.446)mg/L、(4.876±0.569)mg/L;t1/2β分别为(7.489±0.806)h、(7.063±0.890)h、(7.735±0.8701)h;AUC0-t分别为(12.24±1.51)mg·h/L、(26.02±3.38)mg·h/L、(39.22±6.57)mg·h/L;原型药主要经肾排泄,48h尿药累积排泄率分别为(61.90±7.70)%、(60.90±5.70)%和(58.74±13.49)%。结论9名健康受试者分别口服给药后,药-时曲线符合二房室模型,甲磺酸加替沙星在200～600mg剂量范围内药物体内过程呈线性动力学特征而无饱和性,主要排泄途径为肾脏。

Objective To investigate the pharmacokinetics of oral single dose of gatifloxacin mehanesulfanae tablets in Chinese healthy volunteers. Methods The protocol was designed according to GCP principle. The plasma concentrations from the volunteers after oral 200mg, 400mg and 600mg gatifloxacin mehanesulfanae tablets were determined by HPLC method and the pharmacokinetics parameters were calculated by 3P97 software. Results The plasma concentration time curve fits two compartment models after oral gatifloxacin mehanesulfanae 200mg, 400mg and 600mg respectively. The main pharmacokinetic parameters C max were (2 028±0 362)mg/L, (3 749±0 446)mg/L and (4 876±0 569)mg/L; T 1/2β were (7 489±0 806)h, (7 063±0 890)h and (7 735±0 8701)h; AUC 0-t were (12 24±1 51)mg·h/L, (26 02±3 38)mg·h/L and (39 22±6 57) mg·h/L respectively. The cumulative excretion rate of gatifloxacin in urine in 48h were (61 90±7 70)%, (60 90±5 70)% and (58 74±13 49)% respectively. Conclusion The plasma concentration time curve fits two compartment model in 9 healthy volunteers after p.o gatifloxacin mehanesulfanae in single dose (200mg, 400mg or 600mg). It suggested that the process of the drug in human body in the dosage range of 200mg～600mg fit linear dynamic feature and the drug was mainly excreted through kidney.