摘要
目的 :研究加替沙星在中国健康志愿者中的体内过程 ,据此拟定用于中国人的安全有效的给药方案。方法 :加替沙星口服单剂和多剂药代动力学研究分别在 9名和 8名健康志愿者中进行。以高效液相色谱法测定血、尿标本药物浓度。结果 :①受试者单剂空腹口服加替沙星 2 0 0、4 0 0和 6 0 0mg后体内过程均符合血管外二房室模型 ,平均高峰血药浓度分别为 2 .39、4 .2 9和 6 .5 1mg/L ,于给药后 0 .83～ 1.33h到达 ;平均药时曲线下面积 (AUC)分别为 15 .4 4、34.12和 5 4 .95h·mg/L ;平均血清消除半衰期为 7.38、7.82和 7.5 6h ;72h尿中药物平均累积排出率分别为 82 .5 1%、82 .0 3%和 79.15 %。血药浓度和AUC与剂量间呈线性相关 ;②受试者多剂空腹口服加替沙星 4 0 0mg后 ,末剂给药后的体内过程与首剂给药后者相同 ,均符合血管外二房室模型。首剂和末剂给药后的平均高峰血药浓度分别为 3.98mg/L和 4 .76mg/L ;平均达峰时间为 1.5 6h和 1.31h ;平均AUC为 33.5 9h·mg/L和 35 .87h·mg/L ;平均血清消除半衰期为 7.6 0h和 8.0 5h ;除末剂cmax和AUC值均较首剂为高 (P <0 .0 5 )外 ,其余主要药动学参数间的差异均无显著性。③除多剂给药的 1名受试者出现一过性天冬氨酸转氨酶 (AST)及丙氨酸转氨酶(ALT)轻度升高外 。
Objective: To examine the pharmacokinetics of g atifloxacin in Chinese volunteers and work out the dosage regimens for the treat ment of bacterial infections. Methods:Single and multiple dose pharmacokinetic study of gat ifloxacin were conducted in 9 and 8 healthy volunteers respectively. The drug co ncentrations in serum and urine samples were assayed by high performance chromat ography. Results:①The pharmacokinetics of gatifloxacin were fitted in a two compartment open m odel following oral administration of single dose of 200, 400 and 600 mg, the me an peak concentrations in serum being 2.39, 4.29 and 6.51 mg/L,respectively , the mean area under the concentration time curve ( AUC )being 15.44, 34.1 2 and 54.95 h·mg/L and the elimination half life (t 1/2β )being 7.38, 7. 82 and 7.56 h respectively. 82.51%, 82.03% and 79.15% of the doses were excreted in urine within 72 h after an oral dose of 200, 400 and 600 mg. A good linear c orrelation existed between administered doses and serum drug concentrations as w ell as AUCs . ②The pharmacokinetic parameters of gatifloxacin after the firs t and last dose were similar following the 400 mg multiple oral doses study. The peak concentration of the first and last dose were 3.98 mg/L and 4.76 mg/L; rea ched at 1.56 and 1.31 h after dosing, AUC being 33.59 h·mg/L and 35.87 h·m g/L, t 1/2β 7.60 h and 8.05 h respectively. The differences of c max and AUC between the first and last dose being statistically signific ant( P <0.05), there were no significant difference in other pharmacokinetic parameters. ③Only one subject in multiple dose(400 mg)study with transitory elevation of AST and ALT, no laboratory abnormal changes were found. Conclusions:Gatifloxacin is well tolerated, it is rapidly absorb ed with high peak concentration and long elimination half life. Based on the res ults of this study, we suggest gatifloxacin 400 mg once daily for systemic bacte rial infections and 200 mg once daily for lower urinary tract infections to be u sed in phase Ⅱ clinical trial of gatifloxacin.
出处
《中国抗感染化疗杂志》
2003年第5期264-268,共5页
Chinese Journal of Infection and Chemotherapy
