Universität zu Köln

Tragiannidis, Athanasios, Herbrueggen, Heidrun, Ahlmann, Martina, Vasileiou, Eleni ORCID: 0000-0003-4064-8744, Gastine, Silke, Thorer, Heike, Froehlich, Birgit, Mueller, Carsten and Groll, Andreas H. (2019). Plasma exposures following posaconazole delayed-release tablets in immunocompromised children and adolescents. J. Antimicrob. Chemother., 74 (12). S. 3573 - 3579. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2091

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Abstract

Background: Posaconazole is a recommended option for antifungal prophylaxis in paediatric patients >12 years of age. However, little is known about plasma exposures and safety following administration of the delayed-release tablets (DRTs) in children and adolescents. Methods: In a retrospective observational study, we analysed steady-state trough concentrations of posaconazole in all paediatric patients who had received the DRT formulation between May 2015 and December 2018 for antifungal prophylaxis. Dosing was guided by a published population pharmacokinetic model with weight-based dosing. Drug concentrations in plasma were measured by a validated tandem MS method. Liver function and drug discontinuations due to adverse effects were also assessed. Results: A total of 34 patients (21 male, 13 female; median age 12 years, range 5-17 years; median body weight 43.5 kg, range 16-84 kg) undergoing treatment for haemato-oncological disorders (n = 23) or immunosuppression for polyarthritis (n = 1) or post-allogeneic HSCT (n = 11) received posaconazole DRTs for a median of 70days (range 9-391 days). The median first steady-state trough plasma concentration following model-derived dosing was 1607 ng/mL (range 501-8485 ng/mL) with trough concentrations being above the dosing target of >= 700 ng/mL in 32/34 patients (94%). Considering all (first and subsequent) trough concentrations, target attainment was 90% (63/70 samples). Posaconazole was well tolerated without adverse event-related discontinuations or breakthrough infections. Conclusions: Administration of posaconazole DRTs to paediatric patients guided by a population pharmacokinetic-derived dosing algorithm resulted in predictable and potentially effective exposures and was well tolerated over prolonged time periods.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tragiannidis, Athanasios UNSPECIFIED UNSPECIFIED UNSPECIFIED Herbrueggen, Heidrun UNSPECIFIED UNSPECIFIED UNSPECIFIED Ahlmann, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Vasileiou, Eleni UNSPECIFIED orcid.org/0000-0003-4064-8744 UNSPECIFIED Gastine, Silke UNSPECIFIED UNSPECIFIED UNSPECIFIED Thorer, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Froehlich, Birgit UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Groll, Andreas H. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-125872
DOI:	10.1093/jac/dkz359
Journal or Publication Title:	J. Antimicrob. Chemother.
Volume:	74
Number:	12
Page Range:	S. 3573 - 3579
Date:	2019
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2091
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INVASIVE FUNGAL-INFECTIONS; PEDIATRIC-PATIENTS; ANTIFUNGAL PROPHYLAXIS; RESPONSE RELATIONSHIP; VS. FLUCONAZOLE; PHARMACOKINETICS; SAFETY; ITRACONAZOLE; FORMULATION; LEUKEMIA Multiple languages Infectious Diseases; Microbiology; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12587