Interaction between Levofloxacin and Vancomycin in Rats – Study of Serum and Organ Levels

Mori, Hideki; Nakajima, Takeshi; Nakayama, Atumu; Yamori, Motoo; Izushi, Fumio; Gomita, Yutaka

doi:10.1159/000007113

Cited by 13 publications

(10 citation statements)

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“…Mean peak serum concentrations of 35 µg/mL were measured 0.5 h after the last dose of 25 mg/kg BW twice daily for 3 weeks (Haleem et al 2004). However, the plasma half-life of vancomycin in rats in the first 8 h after intravenous injection is short, 1 hour (Mori et al 1998). Thus, the mean vancomycin concentration (3.5 µg/mL) measured in this study 2 h after the last dose is plausible-and is above the MIC for the bacterial strain used.…”

Section: Discussionmentioning

confidence: 99%

Tissue concentrations of vancomycin and Moxifloxacin in periprosthetic infection in rats

et al. 2007

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Section: Discussionmentioning

confidence: 99%

Tissue concentrations of vancomycin and Moxifloxacin in periprosthetic infection in rats

et al. 2007

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“…Adult rats receiving 30 mg/kg of vancomycin subcutaneously had serum levels of 36 g/ml 1 h after administration (2), those receiving 100 mg/kg of vancomycin intravenously had levels of 179.9 g/ml and 44.98 g/ml 0.5 and 2 h after administration, respectively (16), and 25 mg/kg intramuscular of nafcillin resulted in serum levels of 20.6 g/ml (1). Our pups received 15 mg/kg of vancomycin or 50 mg/kg of oxacillin intraperitoneally, and we speculate they had serum levels substantially greater than the MIC of 0.125 g/ml.…”

mentioning

confidence: 99%

Lysostaphin in Treatment of Neonatal Staphylococcus aureus Infection

Oluola

Kong

Fein

et al. 2007

Antimicrob Agents Chemother

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This study describes lysostaphin's effect against methicillin-sensitive Staphylococcus aureus in suckling rats. Standard techniques determined minimal inhibitory and bactericidal concentrations, pharmacokinetics, and efficacy. The numbers of surviving rats after vancomycin, oxacillin, and lysostaphin treatment were comparable and were different from that of controls (P < 0.00001). Lysostaphin appears effective in the treatment of neonatal S. aureus infection.Additional antibacterial agents for staphylococcal infection are needed (3,9,10,12,13,21,27). Lysostaphin, first identified in 1944 (20), is an endopeptidase which specifically cleaves the cell wall cross-linking pentaglycine bridges of Staphylococcus aureus (25) and is active against nondividing organisms (17,19). We describe the effect of lysostaphin against S. aureus in a neonatal animal model.A clinical methicillin-sensitive S. aureus (MSSA) serotype 5 strain (Hernandez) was stored in tryptic soy broth at Ϫ80°C and grown before each experiment. An MSSA strain allowed comparison of lysostaphin to oxacillin and vancomycin. Minimum bactericidal concentrations (MBCs) and MICs of vancomycin, oxacillin, and lysostaphin were determined (7, 18).Fourteen-day timed-pregnancy Wistar rats (Charles River Laboratories) received antibiotic-free water and food ad libitum and delivered at 21 to 22 days of gestation. Pups remained with their dams throughout the experiment. The Baylor College of Medicine Institutional Animal Use Committee approved the research.Three-day-old pups received 1 mg/kg of body weight/dose of lysostaphin at 1, 6, 24, and 30 h. Blood was obtained by cardiac puncture at 1,2,3,7,8,23,25,26,27, 31, 32, 72, and 96 h after the first dose. Three pups' blood was pooled for each data point, and each time point had two data points. Lysostaphin serum concentration was determined by enzyme-linked immunosorbent assay (26).Plates were coated with 100 l (1 g/ml) of rabbit antilysostaphin for 2 h at room temperature and washed with phosphate-buffered saline plus 0.01% Tween 20, and 100 l of standard or sera was added. After 60 min, plates were washed and incubated with biotinylated rabbit antilysostaphin and ExtrAvidin (catalog no. 81K4875; Sigma) for 30 min separately. Substrate tetramethylbenzidine (catalog no. TMBW0100-01; BioFx) was added. Absorbances were measured and converted to concentrations.Three-day-old pups received 0.2 ml subcutaneously (1 ϫ 10 7 CFU/ml) of S. aureus cephalad to the tail. The bacterial concentration was determined by optical density and confirmed by quantitative culture. In the first experiment, littermate pups were randomly assigned to either earlier treatment at 0.5, 6.5, 24, and 30 h after infection or later treatment at 6, 24, 30, and 48 h after infection. Each pup received 0.2 ml intraperitoneally of lysostaphin (1 mg/kg) or an equal volume of normal saline.In the second experiment, littermate pups randomly received 0.2 ml intraperitoneally of lysostaphin (1 mg/kg), vancomycin (15 mg/kg), oxacillin (50 mg/kg), or normal saline ...

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“…[10][11][12][13][14][15][16][17][18] However, commercial production of the TDxFLx series was discontinued, and the global market share of Viva-E is forecasted to surpass that of TDxFLx in the field of analytical chemistry for therapeutic agents and abused drugs. Measurement of VCM concentrations in serum is an essential procedure for pharmacokinetic analysis, and in many cases, serum VCM concentrations were measured by FPIA using TDxFLx or its Standard sera supplemented with the drugs listed in the table were diluted with three-fold volume of drug-free rat serum and applied to EMITand FPIA.…”

Section: Discussionmentioning

confidence: 99%

“…Measurements of serum VCM concentrations were made by EMIT and HPLC for the same samples. [10,11,14,15,17,25] Figure 7 shows the time-course of serum VCM concentrations measured by EMIT.…”

Section: Application To Pharmacokinetic Studymentioning

confidence: 99%

“…However, administration of VCM carries a considerable risk of causing adverse events including nephrotoxicity in spite of excellent antimicrobial efficacy, and this increased risk is dependent on the characteristics of VCM's disposition associated with the degree of its systemic exposure. In these experiments, VCM concentrations in rat serum or plasma were measured by means of various analytical techniques such as fluorescence polarization immunoassay (FPIA), [10][11][12][13][14][15][16][17][18] high performance liquid chromatography (HPLC), [19][20][21][22][23][24][25] liquid chromatography-mass spectrometry (LC-MS), [26,27] and bioassay. [9] From these aspects, a number of pharmacokinetic studies of VCM using rats have been extensively conducted to provide supportive evidence for promoting the appropriate and improved use of this drug.…”

Section: Introductionmentioning

confidence: 99%

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Underestimation of rat serum vancomycin concentrations measured by an enzyme‐multiplied immunoassay technique and the strategy for its avoidance

Konishi

Iga

Nagai

2013

Drug Testing and Analysis

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An enzyme-multiplied immunoassay technique (EMIT) has been widely adopted for the measurement of serum concentrations of vancomycin (VCM) in clinical practice. Because of the growing demand for its application to fundamental pharmacokinetic studies, we examined whether VCM concentrations in rat serum were accurately measured by EMIT. It was found that measured values of known amounts of VCM spiked to rat serum were markedly underestimated with a large analytical variance. When ultrafiltrated rat serum was used as the sample matrix, interference was significantly improved, and the degree of underestimation was attenuated also by diluting samples with physiological saline. These results suggest that endogenous substances of a high molecular weight in rat serum interfere with the analysis of VCM concentrations by EMIT. However, measured values of rat serum VCM concentrations by EMIT were restored to theoretical levels by exposing samples to 70°C for 3-7 min. A likely explanation for the avoidance of interference is that an appropriate thermal force eliminated the immunological function of endogenous substances falsely recognizing VCM without affecting the VCM molecule itself. Regarding serum samples collected from rats that were administered VCM, values measured by EMIT following the heat-treatment agreed well with those by the high performance liquid chromatography (HPLC) method. This is the first report showing interference by endogenous high-molecular substances in the measurement of drug concentrations in rat serum using EMIT. Our findings will contribute to the appropriate use of VCM based on evidence provided by clinical-oriented rat experiments requiring the measurement of serum VCM concentrations by EMIT.

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Interaction between Levofloxacin and Vancomycin in Rats – Study of Serum and Organ Levels

Cited by 13 publications

References 10 publications

Tissue concentrations of vancomycin and Moxifloxacin in periprosthetic infection in rats

Tissue concentrations of vancomycin and Moxifloxacin in periprosthetic infection in rats

Lysostaphin in Treatment of Neonatal Staphylococcus aureus Infection

Underestimation of rat serum vancomycin concentrations measured by an enzyme‐multiplied immunoassay technique and the strategy for its avoidance

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