Interaction between Fluoroquinolones and Bovine Serum Albumin Studied by Affinity Capillary Electrophoresis

Liu, Shiwang; Zhang, Liwei; Zhang, Xin‐Xiang

doi:10.2116/analsci.22.1515

Cited by 26 publications

(14 citation statements)

References 13 publications

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“…The CL r (132 ml/min) of the free drug was greater than the normal glomerular filtration rate (GFR), i.e., 125 ml/min (24), which is suggestive of active renal secretion of the drug. Plasma protein binding was lower than that of existing FQs (10,12,33), indicating a higher percentage of tissue penetration and a lower potential for protein binding-based drug interactions (23).…”

Section: Discussionmentioning

confidence: 83%

Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Nemonoxacin (TG-873870), a Novel Potent Broad-Spectrum Nonfluorinated Quinolone, in Healthy Volunteers

Lin

Chang

Tsai

et al. 2010

Antimicrob Agents Chemother

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Nemonoxacin (TG-873870) is a novel nonfluorinated quinolone with potent broad-spectrum activity against Gram-positive and Gram-negative pathogens, including methicillin-resistant Staphylococcus aureus, penicillinand quinolone-resistant Streptococcus pneumoniae, and vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus. The safety, tolerability, and pharmacokinetics of nemonoxacin were investigated in a double-blind, ascending-single-dose study involving 56 healthy subjects (48 males and 8 females) who were randomly assigned to 1 of 7 dose cohorts. In each successive cohort, two subjects received a placebo and six received single oral doses of 25, 50, 125, 250, 500, 1,000, or 1,500 mg nemonoxacin. Nemonoxacin was well tolerated up to the maximum dose of 1,500 mg. No severe or serious adverse events were observed. The most frequent adverse events were contact dermatitis, pruritus, and erythema. No clinically significant abnormalities were noted in the electrocardiograms, vital signs, or laboratory tests. The plasma concentrations increased over the dose range, and at 500 mg, the free area under the plasma concentration-time curve/MIC 90 ratios and free maximum nemonoxacin concentration/MIC 90 ratios against drug-sensitive/drug-resistant S. pneumoniae and S. aureus were greater than 227 and 24, respectively. The peak time and elimination half-life of nemonoxacin were 1 to 2 h and 9 to 16 h, respectively. The oral clearance was approximately 0.22 liter/h/kg. The plasma protein binding was approximately 16%. The results of this study support further evaluation of the multiple-dose safety, tolerability, and pharmacokinetics of nemonoxacin.Newer-generation quinolones are largely fluoroquinolones (FQs); they are characterized by the presence of a fluorine at the R6 position of the quinolone nucleus (2, 9, 19). Owing to their improved activity against Gram-positive and atypical pathogens, they have been widely used for the treatment and prophylaxis of bacterial infections. However, the use of FQs has been compromised by the emergence of bacterial resistance (3,8,14,18,22,30) and the potential for adverse side effects (15, 21), including ECG QTc interval prolongation, hepatotoxicity, and phototoxicity. Thus, there is an unmet need for newer compounds that are broad-spectrum agents effective against existing bacterial resistance and that have the potential to minimize the risk of use-limiting adverse effects.Nemonoxacin (TG-873870) (36), a novel nonfluorinated quinolone, has recently been developed from a series of 8-methoxy nonfluorinated quinolones (29) as a malate salt. It differs from FQs in that it lacks the fluorine at the R6 position (Fig. 1); this was formerly believed to be important for the antibacterial potency of FQs. Nemonoxacin has demonstrated broadspectrum activity (4, 20, 28) against Gram-positive, Gramnegative, and atypical pathogens. Furthermore, nemonoxacin appears to be more potent than several FQs, including ciprofloxacin, levofloxacin, and moxifloxacin (20). In preclinical studies, ...

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Section: Discussionmentioning

confidence: 83%

Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Nemonoxacin (TG-873870), a Novel Potent Broad-Spectrum Nonfluorinated Quinolone, in Healthy Volunteers

Lin

Chang

Tsai

et al. 2010

Antimicrob Agents Chemother

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“…These other methods have included structural studies based on X-ray crystallography [11] and binding assays based on fluorescence or absorption spectroscopy [19], capillary electrophoresis [20-26], surface plasmon resonance (SPR) [27] and nuclear magnetic resonance (NMR) spectroscopy [28,29]. It is also possible to study these interactions by using chromatographic systems.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Drug Interactions with Serum Proteins by Using High-Performance Affinity Chromatography

Hage

Anguizola

Barnaby

et al. 2011

CDM

138

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The binding of drugs with serum proteins can affect the activity, distribution, rate of excretion, and toxicity of pharmaceutical agents in the body. One tool that can be used to quickly analyze and characterize these interactions is high-performance affinity chromatography (HPAC). This review shows how HPAC can be used to study drug-protein binding and describes the various applications of this approach when examining drug interactions with serum proteins. Methods for determining binding constants, characterizing binding sites, examining drug-drug interactions, and studying drug-protein dissociation rates will be discussed. Applications that illustrate the use of HPAC with serum binding agents such as human serum albumin, α1-acid glycoprotein, and lipoproteins will be presented. Recent developments will also be examined, such as new methods for immobilizing serum proteins in HPAC columns, the utilization of HPAC as a tool in personalized medicine, and HPAC methods for the high-throughput screening and characterization of drug-protein binding.

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“…Binding of some fluoroquinolones with serum albumin has been studied by affinity capillary electrophoresis and continuous ultrafiltration techniques [11,12]. Fluorescence spectroscopic technique has also been used by some workers for the interaction of pefloxacin and ciprofloxacin with serum albumin [13,14].…”

Section: Introductionmentioning

confidence: 99%

Complexation of fluoroquinolone antibiotics with human serum albumin: A fluorescence quenching study

Seedher¹,

Agarwal²

2010

Journal of Luminescence

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Interaction between Fluoroquinolones and Bovine Serum Albumin Studied by Affinity Capillary Electrophoresis

Cited by 26 publications

References 13 publications

Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Nemonoxacin (TG-873870), a Novel Potent Broad-Spectrum Nonfluorinated Quinolone, in Healthy Volunteers

Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Nemonoxacin (TG-873870), a Novel Potent Broad-Spectrum Nonfluorinated Quinolone, in Healthy Volunteers

Characterization of Drug Interactions with Serum Proteins by Using High-Performance Affinity Chromatography

Complexation of fluoroquinolone antibiotics with human serum albumin: A fluorescence quenching study

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