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


METHODS
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.


METHODS
All participants received a single oral dose of 20 mg of atorvastatin.


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.
Kruger
Peter S
PS
Department of Intensive Care, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, Australia. eter_kruger@health.qld.gov.au
Freir
Noelle M
NM
Venkatesh
Bala
B
Robertson
Thomas A
TA
Roberts
Michael S
MS
Jones
Mark
M
D018806:APACHE; D000368:Aged; D000924:Anticholesteremic Agents / Q000097:blood* / Q000493:pharmacokinetics; D000069059:Atorvastatin; D002851:Chromatography, High Pressure Liquid; D003422:Critical Care; D005260:Female; D006538:Heptanoic Acids / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D011446:Prospective Studies; D011758:Pyrroles / Q000097:blood* / Q000493:pharmacokinetics; D018805:Sepsis / Q000097:blood*
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin