Azithromycin concentrations during long-term regimen, a pilot study in patients with MALT lymphoma

Abstract In view of the antineoplastic effects of the macrolide clarithromycin in mucosa associated lymphatic tissue (MALT)-lymphoma, we performed a pilot study assessing levels of azithromycin in plasma, peripheral blood mononuclear cells (PBMC) and polymorphonuclear leukocytes (PMN) of MALT-lympho...

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Autores principales:	Raphael Scheibenpflug, Markus Obermüller, Gottfried Reznicek, Ortrun Neuper, Wolfgang W. Lamm, Markus Raderer, Heimo Lagler
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/65f502612d7b4b8e80d5365453471257
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spelling	oai:doaj.org-article:65f502612d7b4b8e80d53654534712572021-12-02T17:25:43ZAzithromycin concentrations during long-term regimen, a pilot study in patients with MALT lymphoma10.1038/s41598-021-97836-w2045-2322https://doaj.org/article/65f502612d7b4b8e80d53654534712572021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97836-whttps://doaj.org/toc/2045-2322Abstract In view of the antineoplastic effects of the macrolide clarithromycin in mucosa associated lymphatic tissue (MALT)-lymphoma, we performed a pilot study assessing levels of azithromycin in plasma, peripheral blood mononuclear cells (PBMC) and polymorphonuclear leukocytes (PMN) of MALT-lymphoma patients to determine the pharmacokinetics and potential influences of respective concentrations on the therapeutic outcome. In total 16 patients with MALT-lymphoma received 1.5 g of oral azithromycin once-weekly over 6 months. Blood was sampled directly prior to the following dose every 4 weeks during treatment. Drug levels were analysed by high performance liquid chromatography in plasma and intracellularly in PBMC and PMN. They were correlated with patients’ age, weight and body-mass-index and compared between patients responsive or unresponsive to treatment. Mean azithromycin plasma levels of all patients were 58.97 ± 30.48 ng/ml, remaining stable throughout the treatment period. Correlation analysis of plasma azithromycin showed no significance. Intracellular PBMC concentrations were 6648 ± 8479 ng/ml, without any significant difference between responders and non-responders. Mean PMN levels were 39,274 ± 25,659 ng/ml and significantly higher in patients unresponsive to treatment (t = 2.858, p = 0.017). Our drug regime led to continuously high plasma and exceedingly high intracellular concentrations of azithromycin in PBMC and PMN. Age, weight or body-mass-index had no significant influence on plasma levels and thence should not be considered in dosage finding. High AZM levels in PBMC did not lead to a better treatment response, whereas enrichment in PMN suggested a poorer outcome. The threshold for immunomodulatory effects on lymphoma cells might not have been reached. Additionally, the finding of stable plasma and intracellular concentrations over months with high-dose azithromycin administered in intervals might also be important for the further design of azithromycin-based trials against MALT-lymphoma. Trial registration: EudraCT 2016-001521-13, 14/06/2016.Raphael ScheibenpflugMarkus ObermüllerGottfried ReznicekOrtrun NeuperWolfgang W. LammMarkus RadererHeimo LaglerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Raphael Scheibenpflug Markus Obermüller Gottfried Reznicek Ortrun Neuper Wolfgang W. Lamm Markus Raderer Heimo Lagler Azithromycin concentrations during long-term regimen, a pilot study in patients with MALT lymphoma
description	Abstract In view of the antineoplastic effects of the macrolide clarithromycin in mucosa associated lymphatic tissue (MALT)-lymphoma, we performed a pilot study assessing levels of azithromycin in plasma, peripheral blood mononuclear cells (PBMC) and polymorphonuclear leukocytes (PMN) of MALT-lymphoma patients to determine the pharmacokinetics and potential influences of respective concentrations on the therapeutic outcome. In total 16 patients with MALT-lymphoma received 1.5 g of oral azithromycin once-weekly over 6 months. Blood was sampled directly prior to the following dose every 4 weeks during treatment. Drug levels were analysed by high performance liquid chromatography in plasma and intracellularly in PBMC and PMN. They were correlated with patients’ age, weight and body-mass-index and compared between patients responsive or unresponsive to treatment. Mean azithromycin plasma levels of all patients were 58.97 ± 30.48 ng/ml, remaining stable throughout the treatment period. Correlation analysis of plasma azithromycin showed no significance. Intracellular PBMC concentrations were 6648 ± 8479 ng/ml, without any significant difference between responders and non-responders. Mean PMN levels were 39,274 ± 25,659 ng/ml and significantly higher in patients unresponsive to treatment (t = 2.858, p = 0.017). Our drug regime led to continuously high plasma and exceedingly high intracellular concentrations of azithromycin in PBMC and PMN. Age, weight or body-mass-index had no significant influence on plasma levels and thence should not be considered in dosage finding. High AZM levels in PBMC did not lead to a better treatment response, whereas enrichment in PMN suggested a poorer outcome. The threshold for immunomodulatory effects on lymphoma cells might not have been reached. Additionally, the finding of stable plasma and intracellular concentrations over months with high-dose azithromycin administered in intervals might also be important for the further design of azithromycin-based trials against MALT-lymphoma. Trial registration: EudraCT 2016-001521-13, 14/06/2016.
format	article
author	Raphael Scheibenpflug Markus Obermüller Gottfried Reznicek Ortrun Neuper Wolfgang W. Lamm Markus Raderer Heimo Lagler
author_facet	Raphael Scheibenpflug Markus Obermüller Gottfried Reznicek Ortrun Neuper Wolfgang W. Lamm Markus Raderer Heimo Lagler
author_sort	Raphael Scheibenpflug
title	Azithromycin concentrations during long-term regimen, a pilot study in patients with MALT lymphoma
title_short	Azithromycin concentrations during long-term regimen, a pilot study in patients with MALT lymphoma
title_full	Azithromycin concentrations during long-term regimen, a pilot study in patients with MALT lymphoma
title_fullStr	Azithromycin concentrations during long-term regimen, a pilot study in patients with MALT lymphoma
title_full_unstemmed	Azithromycin concentrations during long-term regimen, a pilot study in patients with MALT lymphoma
title_sort	azithromycin concentrations during long-term regimen, a pilot study in patients with malt lymphoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/65f502612d7b4b8e80d5365453471257
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Azithromycin concentrations during long-term regimen, a pilot study in patients with MALT lymphoma

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