多剂量口服甲磺酸加替沙星片在健康志愿者的药代动力学  

Study on pharmacokinetics of multi-dose of oral gatifloxacin methanesulfonate tablets in healthy volunteers

作　　者：裴斐[1] 王睿[1] 方翼[1] 朱曼[1] 柴栋[1] 王中孝[1] 

机构地区：[1]解放军总医院临床药理研究室,北京100853

出　　处：《中国临床药理学杂志》2004年第2期113-116,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的 研究多剂量口服甲磺酸加替沙星片的药代动力学。方法 选择中国健康成年志愿者1 0名,1 8～40岁男性,口服甲磺酸加替沙星片,每次400mg,每日1次,连续10日。用高效液相色谱法测定血药浓度,用3P97软件拟合药代动力学参数。结果 受试者口服甲磺酸加替沙星片,体内过程为二房室模型。连续给药10日后,Auc0-8AUC0-t值比首次给药显著增加,但第10日给药后AUC0-t与首次给药后AUC0-8比较差异无统计学意义。其余参数Cmax,t1/2β,Vd等差异亦无统计学意义。平均稳态血药浓度Cav为0.84±0.18 mg·L-1,稳态血药浓度时间曲线下面积AUCss为26.16±4.53 mg·h·L-1,累积比为1.35±0.87,波动系数1.68±0.16。受试者给药期间未出现严重药物不良反应。结论 本文给药方案,在人体内可达到有效血浆浓度,且连续给药1 0日体内未见蓄积。Objective To investigate the pharmacokinetics of gatifloxacin methanesulfonate after multiple-dose administration in Chinese healthy volunteers. Methods The protocal was designed according to GCP principle. The 10 selected healthy male volunteers in 18-40 year old were administrated 400mg gatifloxacin methanesulfonate once a day for 10 days. The peak and trough concentrations were monitoring everyday. The plasma concentrations were determined by HPLC method and the parameters of pharmacokinetics were calculated by 3P97 software. Results It is two compartment model in vivo after gatifloxacin was administrated in volunteers. The AUC0-8, and AUC0-t, on the 10th day were significantly increased compared with the 1st administration, but there was no significant difference between AUC0-t on 10th day and AUC0-8 on 1st day .The other parameters Cmax t1/2βVd neither. The mean stable concentration Cav was 0.84 ± 0.18 mg·L-1, AUCSS was 26.16±4.53 mg.h-L-1.The accumulation ratio was 1.35±0.87 and fluctuation coefficient was 1.68 ±0.16. There was no significant difference in valley and peak concentrations of 10th day and the 1st day. No serious adverse effect was observed in volunteers. Conclusion Effective concentration in vivo could achieved after intravenous infusion of 400mg gatifloxacin methanesulfonate once a day for 10 days and no accumulation in human body was observed for 10 days administration. The dosing schedule was recommended.

关 键 词：多剂量 口服 甲磺酸加替沙星片 健康志愿者 药代动力学 

分 类 号：R978.19[医药卫生—药品] R969.1[医药卫生—药学]