Pharmacokinetic/pharmacodynamic modelling of the bactericidal activity of free lung concentrations of levofloxacin and gatifloxacin against Streptococcus pneumoniae
Abstract
The aim of this work was to compare the pharmacological properties of levofloxacin and gatifloxacin against Streptococcus pneumoniae by pharmacokinetic/pharmacodynamic (PK/PD) modelling of the time-kill curves employing an E(max) model. An in vitro infection model was used to simulate free pulmonary fluctuating concentrations expected after multiple dosing regimens of both drugs in humans or constant multiples of the minimum inhibitory concentration. PK/PD parameters and PK/PD indices of the simulated dosing regimens were compared. The levofloxacin EC(50) (concentration producing 50% of the maximum effect) (mean ± standard deviation 3.57±2.16 mg/L) was higher than that for gatifloxacin (0.95±0.56 mg/L) when simulating multiple dosing regimens as well as constant concentrations (EC(50,levofloxacin)=2.75±0.45 mg/L; EC(50,gatifloxacin)=1.03±0.52 mg/L). The maximum killing rate constant (k(max)) was not statistically different for both drugs independent of fluctuating (k(max,levofloxacin)=0.40±0.19 h(-1); k(max,gatifloxacin)=0.48±0.15 h(-1)) or constant concentrations (k(max,levofloxacin)=0.34±0.06 h(-1); k(max,gatifloxacin)=0.39±0.23 h(-1)). The PK/PD model was able to describe the effect of levofloxacin and gatifloxacin against S. pneumoniae in vitro for all the simulations investigated. Gatifloxacin was more potent than levofloxacin, but both presented equivalent efficacy. The model can be used for simulating alternative regimens and optimising therapy to treat streptococcal…
Read the paper
Related studies
- Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching
- Penicillins for Treatment of Pneumococcal Pneumonia: Does In Vitro Resistance Really Matter?
- Thiophenes—Naturally Occurring Plant Metabolites: Biological Activities and In Silico Evaluation of Their Potential as Cathepsin D Inhibitors
- Inhalable Mannosylated Rifampicin–Curcumin Co-Loaded Nanomicelles with Enhanced In Vitro Antimicrobial Efficacy for an Optimized Pulmonary Tuberculosis Therapy
- Development and validation of microbial bioassay for quantification of Levofloxacin in pharmaceutical preparations
- Association between cord blood 25-hydroxyvitamin D concentrations and respiratory tract infections in the first 6 months of age in a Korean population: a birth cohort study (COCOA)
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.