Abstract:
:Protein binding of antibacterials in plasma and tissues has long been considered a component of their pharmacokinetic parameters, playing a potential role in distribution, excretion and therapeutic effectiveness. Since the beginning of the 'antibacterial era', this factor has been extensively analysed for all antibacterial classes, showing that wide variations of the degree of protein binding occur even in the same antibacterial class, as with beta-lactams. As the understanding of protein binding grew, the complexity of the binding system was increasingly perceived and its dynamic character described. Studies of protein binding of the fluoroquinolones have shown that the great majority of these drugs exhibit low protein binding, ranging from approximately 20 to 40% in plasma, and that they are bound predominantly to albumin. The potential role in pharmacokinetics-pharmacodynamics of binding of fluoroquinolones to plasma, tissue and intracellular proteins has been analysed, but it has not been established that protein binding has any significant direct or indirect impact on therapeutic effectiveness. Regarding the factors influencing the tissue distribution of antibacterials, physicochemical characteristics and the small molecular size of fluoroquinolones permit a rapid penetration into extravascular sites and intracellularly, with a rapid equilibrium being established between intravascular and extravascular compartments. The high concentrations of these drugs achieved in tissues, body fluids and intracellularly, in addition to their wide antibacterial spectrum, mean that fluoroquinolones have therapeutic effectiveness in a large variety of infections. The tolerability of quinolones has generally been reported as good, based upon long experience in using pefloxacin, ciprofloxacin and ofloxacin in clinical practice. Among more recently developed molecules, good tolerability has been reported for levofloxacin, moxifloxacin and gatifloxacin, but certain other new compounds have been removed from the market because of renal, hepatic and cardiac toxicity. To what extent the protein binding of fluoroquinolones can play a role in their tolerability is unclear. In terms of drug-drug interactions, the role of protein binding is questionable: several drug combinations can be responsible for toxicity, such as with beta-lactams, metronidazole, theophylline, nonsteroidal anti-inflammatory agents or a series of drugs used for cardiac diseases, but protein binding does not seem to be involved in these interactions. In conclusion, protein binding of fluoroquinolones appears to be a complex phenomenon, but has no clear role in therapeutic effectiveness or toxicity.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Bergogne-Bérézin Edoi
10.2165/00003088-200241100-00004keywords:
subject
Has Abstractpub_date
2002-01-01 00:00:00pages
741-50issue
10eissn
0312-5963issn
1179-1926pii
411004journal_volume
41pub_type
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199121040-00004
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journal_title:Clinical pharmacokinetics
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doi:10.2165/00003088-199937010-00001
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更新日期:1996-09-01 00:00:00
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pub_type: 杂志文章,meta分析
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198611010-00002
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journal_title:Clinical pharmacokinetics
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doi:10.2165/00003088-199223020-00007
更新日期:1992-08-01 00:00:00
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journal_title:Clinical pharmacokinetics
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journal_title:Clinical pharmacokinetics
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