Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Oct 2002
Randomized Controlled Trial Multicenter Study Comparative Study Clinical TrialPharmacokinetic-pharmacodynamic analysis of drotrecogin alfa (activated) in patients with severe sepsis.
We aimed to characterize the pharmacokinetics and pharmacodynamics of drotrecogin alfa (activated) (recombinant human activated protein C) in patients with severe sepsis. ⋯ Plasma concentrations of drotrecogin alfa (activated) attain steady state rapidly after the infusion is started and decline rapidly after the infusion is stopped. The infusion rate should be based on predose body weight and not on any other demographic or baseline clinical covariate.
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Clin. Pharmacol. Ther. · Oct 2002
Randomized Controlled Trial Comparative Study Clinical TrialPharmacodynamics of active site-inhibited factor VIIa in endotoxin-induced coagulation in humans.
Inhibition of the tissue factor-factor VIIa pathway attenuated the activation of coagulation and prevented death in a gram-negative bacteremia primate model of sepsis. This lethal animal model suggested that tissue factor also influences inflammatory cascades. ⋯ In summary, ASIS effectively and selectively attenuates tissue factor-induced thrombin generation. Because ASIS was well tolerated, this study provides seminal data to further characterize its anticoagulant and putative anti-inflammatory effects in critically ill patients.