健康志愿者单剂量口服甲磺酸加替沙星胶囊的药代动力学研究

Pharmacokinetics Study of a Single Dose Gatifloxacin Mesylate Capsule in Healthy Volunteers

目的 建立高效液相色谱法测定血浆中加替沙星的药物浓度 ,研究其在人体内的药动学特征。方法 采用Shim packCLC ODSC1 8色谱分析柱 (1 5 0mm× 6mm ,5 μm) ,流动相为甲醇 -水 -十二烷基硫酸钠 (5 0 0ml∶5 0 0ml∶3.5g) ,磷酸调pH =3.0 ;流速1 .0ml/min ;检测波长为 2 92nm。结果 本测定方法的线性范围为 0 .1 5～ 9.92 μg·ml-1 ,r =0 .999,最低检出浓度为 2 0ng·ml-1(按信噪比≥ 3计 ) ,方法平均回收率为 96 .4 0 %～ 97.2 1 % (n =6 ) ,日内RSD在 1 .0 2 %～ 5 .5 6 %之间 ,日间RSD在 1 .6 4 %～ 7.34%之间。药动学研究表明 ,加替沙星体内过程符合一级吸收的一室开放模型 ,Tmax 、Cmax 、T1 / 2 (Ke) 、AUC(0 -2 4h) 分别为 (1 .6 0 4± 0 .4 1 9)h、(3.71 5± 0 .4 2 4 ) μg·ml-1 、(6 .1 4 2± 0 .6 84 )h、(36 .5 6 8± 5 .5 2 2 ) μg·h·ml-1 。结论 口服甲磺酸加替沙星胶囊每次4 0 0mg,每日 1次的给药方案 ,在人体内可达到有效血药浓度。本方法准确快速 ,适用于加替沙星的药动学研究及临床血药浓度监测。

Aim To establish an HPLC method for the plasma concentration of gatifloxacin and investigate its pharmacokinetic features in healthy volunteers.Methods Shim-pack CLC-ODS C 18 (150mm×6mm,5μm) spectrum analytical column was used.Methanol-water-sodium lauryl sulfate (500ml∶500ml∶3.5g,pH=3.0) was adopted as the mobile phase and Flow rate was adjusted at 1.0ml/min with detection wavelength at 292nm.Results HPLC showed that the plasma concentration of gatifloxacin was well in linearity within the ranges of 0.15～9.92μg·ml -1 and the correlation coefficient is 0.999.The limit of detection in plasma was 20ng·ml -1 .The average recovery of the present method was 96.40%～97.21%.The coefficients of inter-day and intra-day variations were 1.02%～5.56% and 1.64%～7.34% respectively.The results showed that the pharmacokinetics of gatifloxacin was in line with the one-compartment open model.The values of T max 、C max 、T 1/2(Ke) 、AUC (0-24h) were (1.604±0.419)h,(3.715±0.424)μg·ml -1 ,(6.142±0.684)h and (36.568±5.522)μg·h·ml -1 respectively.Conclusion Effective concentration in po can be achieved after one dose of 400mg gatifloxacin mesylate per day.The method is accurate and rapid.It can be used to study pharmacokinetics of gatifloxacin mesylate and to monitor the plasma drug concentration.