A preliminary study of atorvastatin plasma concentrations in critically ill patients with sepsis

Kruger, Peter S., Freir, Noelle M., Venkatesh, Bala, Robertson, Thomas A, Roberts, Michael S. and Jones, Mark (2009) A preliminary study of atorvastatin plasma concentrations in critically ill patients with sepsis. Intensive Care Medicine, 35 4: 717-721. doi:10.1007/s00134-008-1358-3


Author Kruger, Peter S.
Freir, Noelle M.
Venkatesh, Bala
Robertson, Thomas A
Roberts, Michael S.
Jones, Mark
Title A preliminary study of atorvastatin plasma concentrations in critically ill patients with sepsis
Journal name Intensive Care Medicine   Check publisher's open access policy
ISSN 0342-4642
1432-1238
Publication date 2009-04-01
Year available 2007
Sub-type Article (original research)
DOI 10.1007/s00134-008-1358-3
Open Access Status
Volume 35
Issue 4
Start page 717
End page 721
Total pages 5
Editor L. Brochard
Place of publication Berlin, Germany
Publisher Springer
Language eng
Subject C1
920109 Infectious Diseases
110305 Emergency Medicine
110310 Intensive Care
030101 Analytical Spectrometry
Abstract Objective: A lack of published pharmacokinetic data on statins in sepsis has prompted concerns about their safety and toxicity. This study determined single dose pharmacokinetics of Atorvastatin administered orally to acutely ill patients. Design, setting and participants: A prospective open label study conducted in a tertiary referral centre on 5 healthy volunteers, 5 acutely ill patients admitted to the medical ward and a heterogeneous cohort of 25 critically ill patients admitted to an intensive care unit. Intervention: All participants received a single oral dose of 20 mg of atorvastatin. Measurement and results: Plasma pharmacokinetics of atorvastatin as measured by maximal plasma concentration (Cmax) and area under the curve (AUC) (0-24) h. Critically ill patients with sepsis had a significantly higher Cmax and AUC as compared to healthy volunteers [110.5(86.5) vs. 5.9(2.50) ng/ml, p < 0.01 and 1,051(810) vs. 67(48) ng h/ml (p < 0.0001)], respectively. Atorvastatin concentrations in the plasma of critically ill patients with sepsis remained supratherapeutic for up to 20 h after a single dose. The AUC was significantly higher for those patients on concomitant CYP 450 inhibitor therapy as compared to those patients not on inhibitors (1,518 +/- 793 vs. 584 +/- 540 ng h/ml, p = 0.0260). Conclusions: Very high plasma concentrations were achieved in intensive care patients with sepsis. This can only be partly explained by altered metabolism of atorvastatin. Further investigations are essential to better describe the pharmacokinetics of statins in various groups of critically ill patients. Caution should be exercised prior to adopting high dose regimens in patients with severe sepsis.
Formatted abstract
Objective
A lack of published pharmacokinetic data on statins in sepsis has prompted concerns about their safety and toxicity. This study determined single dose pharmacokinetics of Atorvastatin administered orally to acutely ill patients.

Design, setting and participants

A prospective open label study conducted in a tertiary referral centre on 5 healthy volunteers, 5 acutely ill patients admitted to the medical ward and a heterogeneous cohort of 25 critically ill patients admitted to an intensive care unit.
Intervention All participants received a single oral dose of 20 mg of atorvastatin.

Measurement and results

Plasma pharmacokinetics of atorvastatin as measured by maximal plasma concentration (Cmax) and area under the curve (AUC) 0–24 h. Critically ill patients with sepsis had a significantly higher Cmax and AUC as compared to healthy volunteers [110.5(86.5) vs. 5.9(2.50) ng/ml, p < 0.01 and 1,051(810) vs. 67(48) ng h/ml (p < 0.0001)], respectively. Atorvastatin concentrations in the plasma of critically ill patients with sepsis remained supratherapeutic for up to 20 h after a single dose. The AUC was significantly higher for those patients on concomitant CYP 450 inhibitor therapy as compared to those patients not on inhibitors (1,518 ± 793 vs. 584 ± 540 ng h/ml, p = 0.0260).

Conclusions

Very high plasma concentrations were achieved in intensive care patients with sepsis. This can only be partly explained by altered metabolism of atorvastatin. Further investigations are essential to better describe the pharmacokinetics of statins in various groups of critically ill patients. Caution should be exercised prior to adopting high dose regimens in patients with severe sepsis.
Copyright Springer-Verlag 2008


Keyword Statin
Pharmacokinetics
Sepsis
Critical illness
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes First published online November 2007

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Tue, 31 Mar 2009, 02:20:14 EST by Maree Knight on behalf of School of Medicine