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 infextions.

A Rapid and Simple High-Performance Liquid Chromatographic Method for Determination of Levofloxacin in Human Plasma

“…In the previous analytical methods [6][7][8][9][10][11][12][13][14][15][16][17], robustness study was not performed. However, in this method, robustness study was conducted to evaluate whether deliberate small changes in HPLC system could or couldn't influence analytical results.…”

“…A validated bioanalytical method for quantitative estimation of LEV in human plasma at a pharmacokinetic range approximately 1-20 µg/mL is necessary to conduct the bioequivalence study [5]. A number of analytical methods for quantifying LEV were developed such as highperformance liquid chromatography coupled with ultraviolet (HPLC-UV), fluorescent (HPLC-FL), and tandem mass spectrometry (HPLC-MS/MS) detector [6][7][8][9][10][11][12][13][14][15][16][17]. Most of these method used many kinds of additives as mobile phase component for improving peak shape and resolution i.e.…”

“…Most of these method used many kinds of additives as mobile phase component for improving peak shape and resolution i.e. triethylamine [7,[12][13][14], bromide [11], tetramethyl ammonium bromide [8], butadiene styrene brominated ammonium [9], tetrabutylammonium hydrogen sulfate [10], and trifluoroacetic acid [6,15]. The other method was developed under gradient elution using a formic acid 0.05% and methanol as mobile phase component [17], but this method gives relatively long separation time (about 13 min).…”

Levofloxacin Cocrystal/Salt with Phthalimide and Caffeic Acid as Promising Solid-State Approach to Improve Antimicrobial Efficiency

“…Levofloxacin hemihydrate (LEV hereafter) is a broad-spectrum antibiotic which is a third-generation fluroquinolone. It is the levo isomer of oflaxacin [ 28 , 29 , 30 ] soluble up to 25 mg/mL in water and having bitter taste [ 31 ]. According to the biopharmaceutical classification system, it has been classified as a class-I drug which has no severe solubility or bioavailability problems [ 32 ].…”

Pharmaceutical organic salt: Disordered crystal structure of levofloxacin with γ-resorcylic acid

“…Pharmaceutical organic salt [9,10] is an important solid-state form of drugs having impact during drug development process. Levofloxacin (LEV), the levo isomer of ofloxacin, is a third generation fluoroquinolone that is used as a broad-spectrum antibiotic for various Gram-positive and Gram-negative organisms [11] and some other pathogens such as Mycoplasma, Chlamydia, Legionella, and Myobacteria spp. [12] are also used for the treatment of chronic bronchitis as well as urinary tract, kidney and skin infections [13] in patients with severe pneumonia and legionnaires disease levofloxacin exerted superior activity [13].…”