Pharmacokinetic study of levofloxacin in rat blood and bile by microdialysis and high-performance liquid chromatography

Cheng, Fu‐Chou; Tsai, Tsung-Yu; Chen, Y.F; Hung, Ling Chien; Tsai, Tung Hu

doi:10.1016/s0021-9673(02)00506-x

Cited by 50 publications

(23 citation statements)

References 21 publications

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“…In our rat model, treatment failure with levofloxacin was correlated with suboptimal fAUC/MIC ratios. These results are similar to those in other animal studies of pneumonia that have evaluated the pharmacodynamics and efficacy of levofloxacin (7,12,15,40). In our model, higher doses of levofloxacin resulted in higher fAUC/MIC ratios and gave levofloxacin efficacy comparable to that of moxifloxacin.…”

Section: Discussionsupporting

confidence: 90%

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Effect of Ethanol on Fluoroquinolone Efficacy in a Rat Model of Pneumococcal Pneumonia

Olsen

Gentry-Nielsen

Yue³

et al. 2006

Antimicrob Agents Chemother

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This investigation compared the effect of ethanol on fluoroquinolone antibiotic efficacy and pharmacodynamics in an ethanol-fed rat model of pneumococcal pneumonia. Male Sprague-Dawley rats received a liquid diet containing 36% of total calories as ethanol. Paired controls (pair-fed controls) were fed a liquid diet without ethanol or received rat chow. Diets began 7 days before and continued for 10 days after transtracheal infections with 10 times the 50% lethal dose of type 3 Streptococcus pneumoniae. Beginning 18 h after infection, the rats received once daily subcutaneous phosphate-buffered saline, levofloxacin, moxifloxacin, or trovafloxacin at 50 or 100 mg/kg of body weight. White blood cell counts were determined, blood samples were collected for culture, and mortality was recorded. Additional rats were killed on day 5 for pharmacodynamic studies and quantitative cultures of bronchoalveolar lavage fluid. Bacteremia occurred by day 3 in 20 of 22 untreated rats. All 22 untreated rats died by day 9. Moxifloxacin treatment was effective in all diet groups at both the 50-and 100-mg/kg doses. In contrast, 50-mg/kg doses of levofloxacin and trovafloxacin improved survival in ethanol-fed rats but were ineffective in chow-fed rats. High-dose trovafloxacin at 100 mg/kg was associated with increased mortality in pair-fed rats. The free-fraction area under the concentration-time curve/MIC ratio exceeded 50 with all antibiotics in the ethanol group but dropped below 30 with levofloxacin and trovafloxacin in the pairand chow-fed rats, with higher mortality. Achievement of adequate antibiotic-free fraction area under the concentration-time curve/MIC ratios helps overcome ethanol-induced immune defects induced in experimental pneumococcal pneumonia.

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Section: Discussionsupporting

confidence: 90%

“…The concentrations of levofloxacin in BAL fluid, BAL cells, and serum were determined by modifications of previously published assays with UV detection (12,60). BAL cells were lysed by freeze-thaw cycles.…”

Section: Methodsmentioning

confidence: 99%

Effect of Ethanol on Fluoroquinolone Efficacy in a Rat Model of Pneumococcal Pneumonia

Olsen

Gentry-Nielsen

Yue³

et al. 2006

Antimicrob Agents Chemother

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“…Some studies are applied to serum [4,5,10,14,26,29,31,34,35], others to plasma [1, 3, 6, 8, 9, 11, 15 -25, 27, 28, 32], and only a few to whole blood [12,13,27]. Only four papers use the solid phase extraction for the pretreatment of blood samples [3,16,21,28].…”

Section: Introductionmentioning

confidence: 99%

Direct determination of five fluoroquinolones in chicken whole blood and in veterinary drugs by HPLC

Samanidou

Christodoulou

Papadoyannis³

2005

J of Separation Science

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A direct, accurate, and sensitive chromatographic analytical method for the quantitative determination of five fluoroquinolones (enoxacin, ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin) in chicken whole blood is proposed in the present study. For quantitative determination lamotrigine was used as internal standard at a concentration of 20 ng/microL. The developed method was successfully applied to the determination of enrofloxacin, as the main component of commercially available veterinary drugs. Fluoroquinolone antibiotics were separated on an Inertsil (250 x 4 mm) C8, 5 microm, analytical column, at ambient temperature. The mobile phase consisted of a mixture of citric acid (0.4 mol L(-1))-CH3OH-CH3CN (87:9:4% v/v) leading to retention times less than 14 min, at a flow rate 1.4 mL min(-1). UV detection at 275 nm provided limits of detection of 2 ng/mL per 20 microL injected volume for enoxacin, norfloxacin, and ciprofloxacin, 0.4 ng/mL for ofloxacin, and 4 ng/mL for enrofloxacin. Preparation of chicken blood samples is based on the deproteinization with acetonitrile while the pharmaceutical drug was simply diluted with water. Peaks of examined analytes in real samples were identified by means of a photodiode array detector. The method was validated in terms of within-day (n=6) precision and accuracy after chicken whole blood sample deproteinization by CH3CN. Using 50 microL of chicken blood sample, recovery rates at fortification levels of 40, 60, and 80 ng ranged from 86.7% to 103.7%. The applicability of the method was evaluated using real samples from chicken under fluoroquinolone treatment.

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“…The blood-to-brain and blood-to-bile is calculated as AUC brain /AUC blood and AUC bile /AUC blood , respectively. Furthermore, these designs have been used to investigate the mechanism of P-glycoprotein [108][109][110][111][112][113][114][115][116][117][118].…”

Section: Resultsmentioning

confidence: 99%

Assaying protein unbound drugs using microdialysis techniques

Tsai

2003

Journal of Chromatography B

115

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Pharmacokinetic study of levofloxacin in rat blood and bile by microdialysis and high-performance liquid chromatography

Cited by 50 publications

References 21 publications

Effect of Ethanol on Fluoroquinolone Efficacy in a Rat Model of Pneumococcal Pneumonia

Effect of Ethanol on Fluoroquinolone Efficacy in a Rat Model of Pneumococcal Pneumonia

Direct determination of five fluoroquinolones in chicken whole blood and in veterinary drugs by HPLC

Assaying protein unbound drugs using microdialysis techniques

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