摘要
目的建立盐酸昌欣沙星在中国健康受试者的药代动力学/药效学(PK/PD)模型并进行仿真,以评价不同给药方案时盐酸昌欣沙星的抑菌效果。方法用LC-MS/MS方法检测单次和连续给药后健康受试者体内的昌欣沙星的血药浓度,并以稳态血药浓度-时间曲线下面积/最低抑菌浓度(AUC/MIC)值作为与盐酸昌欣沙星药效相关的PK/PD指标,通过NONMEM软件建立PK/PD模型,考察300 mg、400 mg及600 mg给药方案下对于6种菌株的药效。结果用二室模型来描述昌欣沙星在健康受试者体内的PK行为。昌欣沙星对于甲氧西林敏感的金黄色葡萄球菌(MSSA)的抑菌效果最佳,300 mg·d-1时AUC/MIC≥1000;对于大肠埃希菌和耐环丙沙星的大肠埃希菌,昌欣沙星在3种给药方案下的AUC/MIC均≤200。结论昌欣沙星作为浓度依赖性药物,提高剂量能在一定程度提高疗效。用建立的PK/PD模型能够预测不同给药方案下昌欣沙星对于不同细菌引起的感染的治疗效果。
Objective To develop pharmacokinetic/pharmacodynamic（ PK/PD） models of chinfloxacin hydrochloride base on the PK data from Chinese health subjects and the PD of antibacterial activities in vitro. To evaluate various administration regimens of chinfloxacin hydrochloride for the bacterial infection based on the established PK/PD models. Methods The plasma concentrations of chinfloxacin hydrochloride after single and continuous administration in health subjects was quantified using LC-MS/MS. The steady-state AUC/MIC was used as the PK/PD indicator correlated with efficacy. The model estimations were performed using NONMEM. The simulation was employed to determine the appropriate regimens of chinfloxacin hydrochloride against the tested 6 clinical isolates of strains. Results A two-compartment model was established to characterize the concentration-time profile of chinfloxacin hydrochloride. Chinfloxacin hydrochloride showed potent bactericidal activity against methiciliin sensitive Staphylococcus aureus（ MSSA）,the regimens of 300 mg · d^（-1） achieved more than 1000 of AUC/MIC. For the Escherichia coli and ciprofloxacin-resistant Escherichia coli,all the designed regimens only achieved less than 200 of AUC/MIC. Conclusion As a dose-dependent antibiotic, the bacteriostatic efficacy ofchinfloxacin hydrochloride can be improved by increasing dose. The developed PK/PD model can be used to predict the clinical outcome of chinfloxacin hydrochloride under different administration regimens.
作者
冀希炜
郑青山
吕媛
JI Xi - wei;ZHENG Qing - shan;LU Yuan(Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100191, China;Center for Drug Clinical Research, Shanghai University Traditional Chinese Medicine, Shanghai 201203, China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2018年第12期1410-1414,共5页
The Chinese Journal of Clinical Pharmacology
关键词
盐酸昌欣沙星
药代动力学/药效学
剂量设计
仿真
ehinfloxacin hydrochloride
pharmaeokinetic/pharmacodynamic
dosing regimens
simulation
