Universität zu Köln

Cornely, Oliver A., Robertson, Michael N., Haider, Shariq, Grigg, Andrew, Geddes, Michelle, Aoun, Mickael, Heinz, Werner J., Raad, Issam, Schanz, Urs, Meyer, Ralf G., Hammond, Sarah P., Mullane, Kathleen M., Ostermann, Helmut, Ullmann, Andrew J., Zimmerli, Stefan, Van Iersel, M. L. P. S., Hepler, Deborah A., Waskin, Hetty, Kartsonis, Nicholas A. and Maertens, Johan (2017). Pharmacokinetics and safety results from the Phase 3 randomized, open-label, study of intravenous posaconazole in patients at risk of invasive fungal disease. J. Antimicrob. Chemother., 72 (12). S. 3406 - 3414. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2091

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Abstract

Objectives: A two-part (Phase 1B/3), sequential, open-label, multicentre study evaluated the pharmacokinetics (PK) and safety of intravenous (iv) posaconazole given as antifungal prophylaxis to neutropenic patients with AML or myelodysplastic syndrome (MDS) or to recipients at risk of invasive fungal disease (IFD) after allogeneic HSCT. Methods: Patients (N=237) received 300mg of posaconazole iv twice daily on day 1, followed by 300mg of posaconazole iv once daily for 4-28 days. After at least 5 days, patients were randomly assigned to receive posaconazole oral suspension, 400mg twice daily or 200mg three times daily, to complete a 28 day treatment course. Primary PK parameters were steady-state average concentration over the dosing interval (C-avg) and posaconazole trough levels (C-min). Results: Mean posaconazole C-min was 1320 ng/mL (day 6) and 1297 ng/mL (day 8); steady-state C-min was 1090 ng/mL (day 10). Mean steady-state posaconazole C-avg was 1500 ng/mL (day 10 or 14) and was similar in HSCT recipients (1560 ng/mL) and AML/MDS patients (1470 ng/mL). The most commonly reported treatment-related adverse events were diarrhoea (8%), nausea (5%) and rash (5%). IFD was reported in 3/237 patients (1%; 2 proven, 1 probable). Conclusions: Intravenous posaconazole at 300mg was well tolerated, resulted in adequate steady-state systemic exposure and was associated with a low incidence of IFD in this population at high risk.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Cornely, Oliver A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Robertson, Michael N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Haider, Shariq UNSPECIFIED UNSPECIFIED UNSPECIFIED Grigg, Andrew UNSPECIFIED UNSPECIFIED UNSPECIFIED Geddes, Michelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Aoun, Mickael UNSPECIFIED UNSPECIFIED UNSPECIFIED Heinz, Werner J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Raad, Issam UNSPECIFIED UNSPECIFIED UNSPECIFIED Schanz, Urs UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer, Ralf G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hammond, Sarah P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mullane, Kathleen M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ostermann, Helmut UNSPECIFIED UNSPECIFIED UNSPECIFIED Ullmann, Andrew J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zimmerli, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Van Iersel, M. L. P. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hepler, Deborah A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Waskin, Hetty UNSPECIFIED UNSPECIFIED UNSPECIFIED Kartsonis, Nicholas A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Maertens, Johan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-210195
DOI:	10.1093/jac/dkx263
Journal or Publication Title:	J. Antimicrob. Chemother.
Volume:	72
Number:	12
Page Range:	S. 3406 - 3414
Date:	2017
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2091
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EXPOSURE-RESPONSE RELATIONSHIP; CELL TRANSPLANT RECIPIENTS; VERSUS-HOST-DISEASE; ORAL POSACONAZOLE; TABLET FORMULATION; HEALTHY-VOLUNTEERS; PROPHYLAXIS; INFECTIONS; FLUCONAZOLE; PLASMA Multiple languages Infectious Diseases; Microbiology; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21019