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Intensive Care Medicine

, Volume 35, Issue 4, pp 717–721 | Cite as

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

  • Peter S. Kruger
  • Noelle M. Freir
  • Bala Venkatesh
  • Thomas A. Robertson
  • Michael S. Roberts
  • Mark Jones
Brief Report

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.

Keywords

Statin Pharmacokinetics Sepsis Critical illness 

Notes

Acknowledgments

This work was supported by a grant from the Princess Alexandra Hospital Research Foundation and Australian National Health and Medical Research Council. Professor Roberts has received a research grant from Pfizer through the University of Queensland for unrelated transdermal research. All other authors have no financial or personal relationships that could inappropriately influence this work. Pfizer has provided no support for this study. All authors have seen and approved the final manuscript version. P. K. was involved in study design, patient enrolment, data analysis and manuscript preparation. N. F. was involved in patient enrolment and sample collection. B. V. was involved in study design, data analysis and manuscript preparation. M. R. was involved in study design, assay quality assurance, data analysis and manuscript preparation. T. R. was involved in assay development and sample analysis. M. J. was involved in the statistical analysis of results.

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Peter S. Kruger
    • 1
    • 2
  • Noelle M. Freir
    • 1
  • Bala Venkatesh
    • 3
  • Thomas A. Robertson
    • 4
  • Michael S. Roberts
    • 4
  • Mark Jones
    • 5
  1. 1.Department of Intensive CarePrincess Alexandra HospitalBrisbaneAustralia
  2. 2.University of QueenslandBrisbaneAustralia
  3. 3.Department of Critical Care, Endocrinology and Metabolism Research UnitUniversity of Queensland, and Princess Alexandra and Wesley HospitalsBrisbaneAustralia
  4. 4.Therapeutics Research UnitUniversity of QueenslandBrisbaneAustralia
  5. 5.School of Population HealthUniversity of QueenslandBrisbaneAustralia

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