Hüttner, Sven

Kinzig, Martina

Krasniqi, Shaip

Matzneller, Peter

Müller, Markus

Sörgel, Fritz

Zeitlinger, Markus

BMC Pharmacology

English

PubMed

Shaip Krasniqi

Peter Matzneller

Martina Kinzig

Sven Hüttner

Fritz Sörgel

Markus Müller

Markus Zeitlinger

Springer - Publisher Connector

MEETING ABSTRACT Open Access
Tissue pharmacokinetics of individual macrolides
support observed differences in development of
bacterial resistance
Shaip Krasniqi1, Peter Matzneller1, Martina Kinzig2, Sven Hüttner2, Fritz Sörgel2, Markus Müller1, Markus Zeitlinger1*
From 16th Scientific Symposium of the Austrian Pharmacological Society (APHAR)
Vienna, Austria. 25-27 November 2010
Background
Recently, differences in development of bacterial resis-
tance were observed for macrolides with short and long
elimination half life. Although one might speculate that
this observation is to be explained by prolonged sub-
inhibitory concentrations at the site of bacterial dwell-
ing, the pharmacokinetic (PK) confirmation of this the-
ory is missing. Thus we set out to compare PK of
azithromycin and erythromycin in plasma, polymorpho-
nuclear leukocytes (PML) and interstitial space fluid
(ISF) of soft tissues.
Methods
Azithromycin (500 mg o.d.) or erythromycin (500 mg q.
i.d.) treatment for three days was randomly administered
to 6 healthy volunteers each. Macrolide concentrations
were determined on day 1 and day 3 (full PK profile)
and on day 5 and 10 (sparse sampling) by tandem mass
spectrometry. Concentrations in ISF of muscle and sub-
cutis were determined by microdialysis.
Results
During active treatment concentrations in plasma and
ISF were higher for erythromycin than for azithromycin,
whereas in white blood cells they were comparable.
Except for azithromycin plasma concentrations and ery-
thromycin PML concentration significant accumulation
was observed for all compartments between single dose
and day 3. For erythromycin concentrations were not
detectable at day 10 for all compartments. In contrast,
azithromycin mean concentrations at day 10 were 8 ± 0
ng/mL in plasma, 9 ± 3 ng/mL in muscle, 4 ± 2 ng/mL
in subcutis and 14,217 ± 2,810 ng/mL in PML.
Conclusions
MIC90 of azithromycin for typical pathogens of the
respiratory tract or soft tissue infections are in the range
of 125–4,000 ng/mL. The present study confirms that
for azithromycin 7 days after end of treatment sub-inhi-
bitory concentrations are present, thereby strongly sup-
porting the hypothesis of increased development of
resistance due to PK reasons. Higher concentrations in
PML than in plasma or ISF indicate that slow back-dis-
tribution from cells into extracellular space is the under-
lying PK mechanism.
Author details
1Department of Clinical Pharmacology, Medical University of Vienna, 1090
Vienna, Austria. 2Institute for Biomedical and Pharmaceutical Research, 90562
Nürnberg-Heroldsberg, Germany.
Published: 16 November 2010
doi:10.1186/1471-2210-10-S1-A45
Cite this article as: Krasniqi et al.: Tissue pharmacokinetics of individual
macrolides support observed differences in development of bacterial
resistance. BMC Pharmacology 2010 10(Suppl 1):A45.
* Correspondence: markus.zeitlinger@meduniwien.ac.at
1Department of Clinical Pharmacology, Medical University of Vienna, 1090
Vienna, Austria
Full list of author information is available at the end of the article
Krasniqi et al. BMC Pharmacology 2010, 10(Suppl 1):A45
http://www.biomedcentral.com/1471-2210/10/S1/A45
© 2010 Zeitlinger et al; licensee BioMed Central Ltd.


Tissue pharmacokinetics of individual macrolides support observed differences in development of bacterial resistance

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Tissue pharmacokinetics of individual macrolides support observed differences in development of bacterial resistance

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