甲磺酸帕珠沙星的人体药动学研究

Pharmacokinetics of Pazufloxacin Mesilate in Chinese Healthy Volunteers

目的研究甲磺酸帕珠沙星在健康志愿者体内的药动学。方法9名健康志愿者按拉丁方设计交叉静脉滴注甲磺酸帕珠沙星150,300和500 mg,用HPLC-荧光法测定血药浓度,用3P87软件计算药动学参数,用SPSS11.0软件和SAS6.12软件进行统计分析处理。结果甲磺酸帕珠沙星的药动学符合二室开放模型。3种不同剂量的药动学参数:t1/2β分别为(1.90±0.47),(1.71±0.48)和(1.60±0.26)h;ρmax分别为(3.22±1.20),(6.62±2.39)和(11.07±3.86)mg.L-1;AUC0-12 h分别为(4.93±1.23),(11.36±2.10)和(18.13±4.50)mg.h.L-1;AUC0-∞分别为(5.01±1.22),(11.56±2.13)和(18.28±4.52)mg.h.L-1;CLs分别为(33.20±7.48),(28.23±4.67)和(30.74±9.61)L.h-1;Vd分别为(17.83±9.44),(24.66±14.63)和(20.10±14.24)L;MRT0-12 h分别为(2.03±0.35),(2.11±0.20)和(2.10±0.27)h;MRT0-∞分别为(2.28±0.43),(2.35±0.38)和(2.21±0.32)h。上述参数在男、女性别间均无显著差异(P>0.05)。除ρmax,AUC0-12 h和AUC0-∞外其他参数均无剂量差异。ρmax,AUC0-12 h和AUC0-∞均与剂量呈线性相关。结论甲磺酸帕珠沙星具有线性药动学特征,其药动学参数无男、女性别差异,在临床给药时无需考虑性别问题。

OBJECTIVE To investigate the pharmacokinetics of pazufloxacin mesilate in Chinese healthy volunteers. METHODS 9 healthy volunteers were divided into 3 groups randomly. Each one was given 150,300 and 500 mg of pazufloxacin mesilate in a given order, respectively. A HPLC method was established for the determination of plasma pazufloxacin mesilate concentration. 3P87 software was used for the analysis of phannacokinetic parameters. SPSS11.0 and SAS6.12 software were used for statistic analysis. RESULTS The pharmacokinetics of pazufloxacin mesilate was discribed by a two-compartment open model. Pharmacokinetic parameters for three different dosages were as follows： t1/2β（1.90± 0.47）, （1.71±0.48） and（ 1.60 ± 0.26） h; ρmax （3.22 ± 1.20）, （6.62 ± 2.39） and（ 11.07± 3.86） mg·L^-1; AUC0-12 h （4.93±1.23）,（11.36±2.10） and （18.13±4.50） mg·h·L^-1;AUC0-∞ （5.01±1.22）,（11.56±2.13） and （18.28±4.52）mg·h·L^-1; CLs（33.20±7.48）,（28.23±4.67） and （30.74±9.61） L-h-l; Vd（17.83±9.44） , （24.66±14.63） and （20.10±14.24） L; MRT0-12h （2.03±0.35）,（2.11±0.20） and（2.10±0.27） h;MRT0-∞ （2.28±0.43）, （2.35±0.38） and（2.21±0.32） h, respectively. There was no statistically significant difference between male and female volunteers. Except ρmax, AUC0-12h and AUC0-∞, no statistically significant difference was obtained among different dosages. There were linear correlation between ρmax, AUC0-12h, AUC0-∞ and dosage. CONCLUSION Pazufloxacin mesilate is characterized by linear pharmacokinetics, it can be safely used for the control of infection.