ABSTRACT: ObjectiveA 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 participantsA 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.
InterventionAll participants received a single oral dose of 20mg of atorvastatin.
Measurement and resultsPlasma pharmacokinetics of atorvastatin as measured by maximal plasma concentration (Cmax) and area under the curve (AUC)
0–24h. 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)ngh/ml (p<0.0001)], respectively. Atorvastatin concentrations in the plasma of critically ill patients with sepsis remained supratherapeutic
for up to 20h 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±540ngh/ml, p=0.0260).
ConclusionsVery 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.
Intensive Care Medicine 04/2012; 35(4):717-721. · 5.40 Impact Factor