Posaconazole Plasma Concentrations : Correlation of Early Trough Levels (day 4) with Steady -State Concentrations

Ref ID: 19547

Author:

M Hoenigl1*, W Duettmann2, K Seeber1, A Wölfler2, B Huber-Krassnitzer2, J Prattes1, K Troppan2,
R Raggam3, H Semmelrock3, F Prüller3, J Wagner1, R Krause1

Author address:

1Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University
of Graz, Graz, Austria
2Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
3Clinical Institu

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Purpose:
Low posaconazole plasma concentrations (PPCs) may be associated with breakthrough invasive
mould infections (IMI) among patients with hematological malignancies. Generally it is considered
that steady-state plasma concentrations of posaconazole are achieved after 6 to 10 days. The purpose
of this study was to correlate PPCs measured early (day 4 of prophylaxis) with those obtained during
steady state.
Methods:
The study was conducted at the Division of Hematology, Medical University of Graz, Austria.
Hematologic patients receiving posaconazole with initial trough PPCs obtained on day 4 of
prophylaxis and then subsequent PPCs obtained between day 7 and 8 (defined as “œearly steady
state”) as well as between days 10 and 14 (defined as “œlate steady state”) were included. The two
steady state time points were always compared to concentrations of day 4. PPCs above the target of
0.5 mg/L were defined as satisfactory and those below the target as low PPCs.
Results:
A total of 37 patients with PPCs obtained at all 3 time points were included. 8 patients (22%) had
PPCs below 0.2 on day 4. PPCs remained unchanged in all patients at early steady state, while at
late steady state 1/8 had a satisfactory PPC and 3/8 PPCs between 0.2 and 0.4. 11 patients (30%)
had PPCs between 0.2 and 0.5 at day 4. At early steady state 2 of those 11 patients had satisfactory
levels and one a PPC <0.20, while PPCs remained unchanged in 8/11 patients. At late steady state PPCs had decreased in 2 to <0.20 and increased in 3 to >0.50, while they remained unchanged in
6/11 patients. The majority of included patients (n=18; 49%) had satisfactory PPCs on day 4. PPCs
decreased below 0.5 in 4/18 patients at early and 3/18 patients at late steady state (each compared to
day 4). Concentrations remained satisfactory in 14/18 patients at early steady state and 15/18 patients
at late steady state, although accumulating to twice or more of the initial day 4 PPC in 4 patients at
early and 6 at late steady state.
Conclusion:
A positive correlation was found between PPCs obtained on day 4 and those on days 7/8 and 10-14.
In patients with insufficient PPCs on day 4 only 4/19 had satisfactory PPCs at late steady-state. In
patients with PPCs >0.5 on day 4 concentrations remained satisfactory in nearly 80% at both steadystate
time points. Bigger studies are needed to evaluate potential benefits of early PPC measurements
and early intervention (e.g. modification of intake procedure and dosage).

Abstract Number: 74

Conference Year: 2014

Link to conference website: http://www.AAA2014.org

New link: NULL

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