ABSTRACTS from 16th International COnference on ... - CRRT Online

<strong>ABSTRACTS</strong> FROM 17 TH INTERNATIONAL CONFERENCE ON CRRT,
SAN DIEGO, FEB 14-17, 2012
69. Plasma and Tissue
Pharmacokinetics of Meropenem
in Critically Ill patients on
Continuous Renal Replacement
Therapy
Julie M Varghese, Paul Jarrett, Suzie L
Parker-Scott, Steven C Wallis, Jeffrey
Lipman, Jason A Roberts
Burns, Trauma and Critical Care
Research Centre, The University of
Queensland, Brisbane, Queensland,
Australia, Department of Intensive Care
Medicine, Royal Brisbane and Women's
Hospital, Brisbane, Queensland,
Australia
Background: For carbapenems, a
minimum time above MIC (T>MIC) of
4% or preferably 1% of the dosing
interval is required to ensure maximal
antibiotic efficacy. This study examined
the plasma and tissue pharmacokinetics
of meropenem in critically ill patients
undergoing continuous veno-venous
haemodiafiltration (CVVHDF).
Methods: This was a prospective
pharmacokinetic study in 5 critically ill
patients on CVVHDF. CVVHDF was
performed as a 2-3 L/h exchange using a
polyacrylonitrile filter with a surface
area of 1.5 m2 and a blood flow rate of 2
mL/min. Meropenem 5 mg was
administered 8-hourly as an IV bolus
infusion over 3 minutes. Serial blood
samples (pre- and post-filter) and
filtrate/dialysate samples were collected
for analysis. Tissue concentrations were
also measured using microdialysis.
Meropenem concentrations were
measured using a validated assay
method. Pharmacokinetic analysis was
conducted using a non-compartmental
approach. Results: Three males and two
females were enrolled with a median age
of 63 (inter-quartile range 48-63) years
and weight 1 (68-12) kg. Four of the five
patients were sampled on two occasions
(Profile A and B). The pharmacokinetic
parameters for meropenem are reported
in the Table. The concentration-time
profile of meropenem in plasma and
tissues is presented in the Figure below.
%age T>MIC during the dosing interval
was calculated to be 1% for MICs of 2
and 4 mg/L and 64% for MIC of 8 mg/L.
Conclusion: Based on our plasma and
tissue pharmacokinetic data, meropenem
5 mg 8-hourly dosing appears
appropriate using our dialysis settings.
Pharmacokinetic parameter Profile A Median (IQR)
Profile B Median
(IQR)
Peak plasma concentration
(mg/L)
4.74 (36.56-45.56) 35.96 (27.49-44.93)
Trough plasma concentration
(mg/L)
4.89 (3.48-4.99) 5.35 (4.16-6.46)
Plasma elimination half life (h) 3.71 (3.29-4.1) 3.75 (3.6-4.15)
Volume of distribution (L/kg) .26 (.17-.35) .25 (.23-.29)
Total clearance (L/h) 4.12 (4.11-4.79) 3.81 (3.16-4.75)
CVVHDF clearance (L/h) 2.91 (2.73-3.12) 2.8 (2.31-3.33)
Peak tissue concentration
(mg/L)
13.6 (11.97-16.84) 18.3 (15.88-18.68)
Trough tissue concentration
(mg/L)
2.59 (2.38-3.36) 3.66 (2.57-4.96)
AUC tissue: AUC plasma .63 (.6-.69) .69 (.64-.74)
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