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Clinical Pharmacokinetics

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01-02-2009 | Review Article

Penetration of Antibacterials into Bone

Pharmacokinetic, Pharmacodynamic and Bioanalytical Considerations

Authors: Cornelia B. Landersdorfer, Jürgen B. Bulitta, Martina Kinzig, Ulrike Holzgrabe, Prof. Dr Fritz Sörgel

Published in: Clinical Pharmacokinetics | Issue 2/2009

Abstract

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<0.05) concentration ratios than linezolid. For 20 of 25 different drugs, the ratios were higher for cancellous bone than for cortical bone.

The available data show a larger extent of bone penetration for quinolones, macrolides and linezolid than for β-lactams. The bone penetration of penicillins and cephalosporins was significantly lower than that of linezolid. Guidelines on sample preparation, drug analysis, study design and pharmacokinetic evaluation of bone penetration studies are vitally needed.

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Title: Penetration of Antibacterials into Bone
Pharmacokinetic, Pharmacodynamic and Bioanalytical Considerations
Authors: Cornelia B. Landersdorfer
Jürgen B. Bulitta
Martina Kinzig
Ulrike Holzgrabe
Prof. Dr Fritz Sörgel
Publication date: 01-02-2009
Publisher: Springer International Publishing
Published in: Clinical Pharmacokinetics / Issue 2/2009
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.2165/00003088-200948020-00002

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Penetration of Antibacterials into Bone

Pharmacokinetic, Pharmacodynamic and Bioanalytical Considerations

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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