Pharmacokinetics of Telithromycin in Plasma and Soft Tissues after Single-Dose Administration to Healthy Volunteers

Gattringer, Rainer; Urbauer, Eleonora; Traunmüller, Friederike; Zeitlinger, Markus; Dehghanyar, Pejman; Zeleny, Petra; Graninger, Wolfgang; Müller, Markus; Joukhadar, Christian

doi:10.1128/aac.48.12.4650-4653.2004

Cited by 25 publications

(27 citation statements)

References 23 publications

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“…However, all these parameters cannot explain the discrepancy between the results of the single-dose part and the multiple-dose part of the present study because no significant change in pK a , the pH of the tissue, or the octanol/water partition coefficient is expected to occur between single and multiple doses in our healthy study population. Thus, our observation is not yet fully understood, but it should be mentioned that similar behaviors were found by our group for gemifloxacin (9) and telithromycin (7). This underlines the need for novel strategies for the investigation of the tissue pharmacokinetics of antibiotics.…”

Section: Discussionmentioning

confidence: 80%

Penetration of Linezolid into Soft Tissues of Healthy Volunteers after Single and Multiple Doses

Dehghanyar

Bürger

Zeitlinger

et al. 2005

Antimicrob Agents Chemother

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The present study tested the ability of linezolid to penetrate soft tissues in healthy volunteers. Ten healthy volunteers were subjected to linezolid drug intake at a dose of 600 mg twice a day for 3 to 5 days. The first dose was administered intravenously. All following doses were self-administered orally. The tissue penetration of linezolid was assessed by use of in vivo microdialysis. In the single-dose experiments the ratios of the area under the concentration-time curve from 0 to 8 h (AUC 0-8 ) for tissue to the AUC 0-8 for free plasma were 1.4 ؎ 0.3 (mean ؎ standard deviation) and 1.3 ؎ 0.4 for subcutaneous adipose and muscle tissue, respectively. After multiple doses, the corresponding mean ratios were 0.9 ؎ 0.2 and 1.0 ؎ 0.5, respectively. The ratios of the AUC from 0 to 24 h (AUC 0-24 ) for free linezolid in tissues to the MIC were between 50 and 100 for target pathogens with MICs between 2 and 4 mg/liter. In conclusion, the present study showed that linezolid penetrates rapidly into the interstitial space fluid of subcutaneous adipose and skeletal muscle tissues in healthy volunteers. On the basis of pharmacokinetic-pharmacodynamic calculations, we suggest that linezolid concentrations in soft tissues can be considered sufficient to inhibit the growth of many clinically relevant bacteria.

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Section: Discussionmentioning

confidence: 80%

Penetration of Linezolid into Soft Tissues of Healthy Volunteers after Single and Multiple Doses

Dehghanyar

Bürger

Zeitlinger

et al. 2005

Antimicrob Agents Chemother

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“…Like tigecycline, telithromycin displays extensive tissue distribution, with a volume of distribution of 2.9 L/kg [87,89], suggesting that concentrations may be higher at the site of action. This is also supported by a microdialysis study in healthy volunteers with telithromycin that found AUC 0-8 ratios of free tissue/free plasma of 2.1 ± 1.6 and 1.5 ± 0.9 for subcutaneous adipose and muscle tissue, respectively [90]. Another explanation for a low PK/PD targeted index is that these antibiotics accumulate intracellularly, especially azithromycin and telithromycin [91][92][93].…”

Section: Macrolides Ketolides and Azalidesmentioning

confidence: 91%

Class-dependent relevance of tissue distribution in the interpretation of anti-infective pharmacokinetic/pharmacodynamic indices

Barbour

Scaglione

Derendorf

2010

International Journal of Antimicrobial Agents

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“…Telithromycin achieves high and prolonged concentrations in the lung (Kadota et al 2002 ;Khair et al 2001 ), nasal mucosa and ethmoid bone (Kuehnel et al 2005 ), tonsils (Gehanno et al 2003 ), female genital tract (Mikamo et al 2003 ), and infl amed blister fl uid (Namour et al 2002 ). Its free concentration in soft tissues (subcutis and muscle) is close to the free serum concentration (Gattringer et al 2004 ;Traunmuller et al 2009 ).…”

Section: Distributionmentioning

confidence: 94%

Macrolides and Ketolides

Bambeke

2013

Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics

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Macrolides and ketolides are characterized by a very wide tissular distribution, which is related to their capacity to accumulate in the acidic compartments of the cells. This property is considered an advantage, because it concentrates the drug at the site of infection. Yet, the low serum levels consecutive to this tissular distribution may favor the selection of resistance. Macrolides are essentially bacteriostatic and ketolides are slowly bactericidal. The pharmacodynamic indice that best predicts effi cacy is the free 24 h-AUC/MIC ratio for both subclasses. Despite their high concentration inside the cells, macrolides and ketolides remain bacteriostatic against intracellular bacteria, with a potency similar to that observed extracellularly. New formulations have been developed to optimize patient's adherence (extended release tablets) or to further increase antibiotic concentration at the site of infection (powders for inhalation).

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Pharmacokinetics of Telithromycin in Plasma and Soft Tissues after Single-Dose Administration to Healthy Volunteers

Cited by 25 publications

References 23 publications

Penetration of Linezolid into Soft Tissues of Healthy Volunteers after Single and Multiple Doses

Penetration of Linezolid into Soft Tissues of Healthy Volunteers after Single and Multiple Doses

Class-dependent relevance of tissue distribution in the interpretation of anti-infective pharmacokinetic/pharmacodynamic indices

Macrolides and Ketolides

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