Penetration of Antibacterials into Bone: Pharmacokinetic, Pharmacodynamic and Bioanalytical Considerations

Antibacterials play a key role in the treatment of bone infections and appropriate surgical prophylaxis. The rate and extent of penetration of antimicrobials into bone has been assessed and shown to be important for successful treatment in numerous studies. However, no recent review or critical eval...

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Bibliographic Details
Published in:Clinical pharmacokinetics 2009-01, Vol.48 (2), p.89-124
Main Authors: Landersdorfer, Cornelia B., Bulitta, Jürgen B., Kinzig, Martina, Holzgrabe, Ulrike, Sörgel, Fritz
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - metabolism
Anti-Bacterial Agents - pharmacokinetics
Anti-Bacterial Agents - pharmacology
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
beta-Lactams - metabolism
beta-Lactams - pharmacokinetics
beta-Lactams - pharmacology
Biological and medical sciences
Bone and Bones - metabolism
Clinical Trials as Topic - methods
General pharmacology
Glycopeptides - metabolism
Glycopeptides - pharmacokinetics
Glycopeptides - pharmacology
Humans
Injections, Intravenous
Internal Medicine
Macrolides - metabolism
Macrolides - pharmacokinetics
Macrolides - pharmacology
Medical sciences
Medicine
Medicine & Public Health
Models, Biological
Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
Pharmacology. Drug treatments
Pharmacology/Toxicology
Pharmacotherapy
Quinolones - metabolism
Quinolones - pharmacokinetics
Quinolones - pharmacology
Review Article
Structure-Activity Relationship
Surgical Wound Infection - metabolism
Surgical Wound Infection - prevention & control
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Summary:Antibacterials play a key role in the treatment of bone infections and appropriate surgical prophylaxis. The rate and extent of penetration of antimicrobials into bone has been assessed and shown to be important for successful treatment in numerous studies. However, no recent review or critical evaluation of the analytical techniques is available. This review compares established and new sample preparation and analytical methods to measure bone concentrations. We performed a systematic literature search in MEDLINE, EMBASE, conference abstracts and references from published articles on bone penetration of antibacterials. This article focuses on the standardization of drug analysis in bone, the extent and rate of bone penetration of antibacterials, and the design, evaluation and reporting techniques of pharmacokinetic studies of bone penetration. The focus is on studies conducted between 1998 and 2007, since a previous review was published in 1999. WinNonlin® Professional version 5.0.1 software was used for statistics. Very different methods for sample preparation, drug analysis, data handling and reporting have been employed in bone penetration studies. There is substantial variability in the reported mean bone penetration between drugs and between different studies of the same drug. Quinolones, macrolides and linezolid have mean bone:serum concentration ratios that are commonly between 0.3 and 1.2, and higher ratios have been found for azithromycin (bone concentration in mg/kg of total bone). The ratios are usually between 0.15 and 0.3 for cephalosporins and glycopeptides, and between 0.1 and 0.3 for penicillins. Cephalosporins and penicillins have shown significantly lower (p
ISSN:0312-5963
1179-1926
DOI:10.2165/00003088-200948020-00002