Pharmacokinetic and pharmacodynamic analysis of flomoxef against the clinical isolates of strains
10.13699/j.cnki.1001-6821.2017.11.014
- VernacularTitle:氟氧头孢对临床菌株的药代动力学及药效学研究
- Author:
Xi-Wei JI
1
;
Yuan L(U)
;
Yun LI
;
Wei LU
Author Information
1. 北京大学第一医院临床药理研究
- Keywords:
flomoxef;
pharmacokinetic/pharmacodynamic;
dosing regimens;
probability of target attainment;
Monte Carlo simulation
- From:
The Chinese Journal of Clinical Pharmacology
2017;33(11):1007-1012
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the optimal administration regimen of flomoxef for the bacterial infection based on pharmacokinetic/pharmacodynamic (PK/PD) models.Methods A literature search was conducted in PubMed to capture the pharmacokinetic data of flomoxef.Minimum inhibitory concentrations (MICs) were determined using two-fold agar dilution method.The percent time that drug concentration exceeds the minimum inhibitory concentration (％fT＞MIC) was used as the PK/PD indicator correlated with efficacy.Monte Carlo simulation was employed to determine the appropriate regimens of flomoxef based on the probability of target attainment (PTA) against the clinical isolates of strains.Results The regimens of 1 g q6 h,1 g q8 h and 1 g q12 h with 1 hour infusion at 70％ of ％ fT＞MIC achieved 93.1％,89.1％ and 66.8％ of PTA against Escherichia coli (ESBL +),respectively.For the Klebsiella pneumoniae (ESBL+),these regimens achieved 81.8％,78.7％ and 62.3％ of PTA at ％fT＞MIC =70％.The regimen of 2 g q12 h achieved the similar PTA as 1g q6 h and 1 g q8 h at 50％ and 70％ of ％fT＞MIC,but not at higher ％ fT＞MIC.Furthermore,flomoxef also showed potent bactericidal activity against Escherichia coli (ESBL-),Klebsiella pneumoniae (ESBL-),methicillin-susceptible S.aureus (MSSA),methicillin-susceptible S.Epidermidis (MSSE) and Moraxella catarrhalis,etc.with all dosing regimens according to the PK/PD analysis.Conclusion As a time-dependent antibiotic,the clinical outcome of flomoxef can be improved by shortening dosing interval,extending infusion time and/or increasing dose.The first two strategies played more significant roles.
