Pharmacokinetics of Caspofungin in Intensive Care Unit Patients

Ref ID: 19290

Author:

E. W. Muilwijk, J. Schouten, H. J. van Leeuwen, A. van Zanten, D. W. de Lange, A. Colbers, P. E. Verweij, D. M. Burger, P. Pickkers, R. J. Brüggemann

Author address:

Radboud Univ. Nijmegen Med. Ctr., Nijmegen, NETHERLANDS,
Canisius Wilhelmina Hosp., Nijmegen, NETHERLANDS,
Rijnstate Hosp., Arnhem, NETHERLANDS, Hosp. Gelderse Vallei, Ede, NETHERLANDS, Univ. Med. Ctr. Utrecht, Utrecht, NETHERLANDS.

Full conference title:

53rd Interscience Conference on Antimicrobial Agents and Chemotherapy

Date: 10 September 2014

Abstract:

Background: PK of antimicrobial agents in ICU patients can be highly variable. We set out to explore caspofungin (CAS) PK in ICU patients. Methods: ICU patients (from 5 hospitals) receiving CAS as antifungal treatment were eligible. Patients received a loading dose of 70mg followed by 50mg QD (70mg if bodyweight >80kg); they were evaluable when a PK curve on day 3 was completed. In addition, daily trough samples and a PK curve on day 7 were taken. Samples were measured by a validated UPLC-fluorescence method. PK analysis was performed using a standard two-stage approach (Phoenix and SPSS). AUC on day 7 was compared to day 3 using a paired T-test on the log-transformed AUC values.Results: 19 out of 22 patients (8 female, 11 male) were evaluable. Median (range) age and bodyweight was 73 (45-80) yr and 74 (50-99) kg. PK sampling on day 3 (n=19) resulted in a median CAS AUC0-24h of 88.7 (IQR 76.1-96.6) mg*h*L-1, a median Cmin of 2.15 (IQR 1.42-2.33) mg/L, a median Cmax of 7.51 (IQR 6.08-8.23) mg/L, a median Vd of 7.72 (IQR 6.08-9.28) L and a median CL of 0.57 (IQR 0.54-0.73) L*h-1. PK sampling on day 7 (n=12) resulted in a median AUC0-24h of 111.7 (IQR: 93.7-126.9) mg*h*L-1, a median Cmin of 2.65 (IQR 2.03-3.09) mg/L, a median Cmax of 8.73 (IQR 6.95-9.39) mg/L, a median Vdof 6.49 (IQR 5.46-7.65) L and a median CL of
0.52 (IQR 0.42-0.58) L*h-1. AUCday7 was significantly higher
than AUCday3 (n=10, p=0.03); visual inspection of daily
trough concentrations revealed a slight increase over time,
suggesting steady state was not reached on day 3. We did
not identify any significant covariates on CAS PK (e.g.
bodyweight, albumin, liver function). CAS was safe and
well tolerated. Conclusions: CAS PK in ICU patients shows
limited inter- and intravariability and was well tolerated.
Our study shows similar CAS PK in ICU patients compared
to CAS PK in non-critically ill patients. Standard two-stage
approach did not reveal significant covariates. Non Linear
Mixed Effect Modeling will be performed with this data set.

Abstract Number: NULL

Conference Year: 2013

Link to conference website: NULL

New link: NULL

Conference abstracts, posters & presentations

Showing 10 posts of 17325 posts found.

  • Title

    Author

    Year

    Number

    Poster