title: Effects of drotrecogin alfa (activated) in human endotoxemia.
abstract: In a phase III clinical trial, drotrecogin alfa (activated) was shown to improve survival and promote faster improvement of cardiovascular and respiratory dysfunction in patients with severe sepsis. To further examine mechanisms involved in the action of this drug, a healthy human endotoxin model was used. Healthy volunteers (eight per group) received drotrecogin alfa (activated) or placebo intravenously for 8 h in a randomized, double-blind, controlled manner. After 2 h of study drug infusion, endotoxin (2 ng/kg) was infused and measurement of physiologic responses and biomarkers continued for 24 h. Consistent with results from severe sepsis clinical trials, drotrecogin alfa (activated) improved mean arterial pressure during the period of infusion after endotoxin exposure. In contrast to severe sepsis clinical trials using drotrecogin alfa (activated) but similar to another human endotoxin study, no significant antithrombotic, profibrinolytic, or anti-inflammatory effects were observed. These results suggest a novel role for drotrecogin alfa (activated) in the human endotoxin model.
authors.affiliation: UMDNJ-Robert Wood Johnson Medical School, Department of Surgery, New Brunswick, New Jersey 08903, USA.
authors.forename: Andre C
authors.initials: AC
authors.lastname: Kalil
authors.forename: Susette M
authors.initials: SM
authors.lastname: Coyle
authors.forename: John Y
authors.initials: JY
authors.lastname: Um
authors.forename: Steven P
authors.initials: SP
authors.lastname: LaRosa
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Turlo
authors.forename: Steve E
authors.initials: SE
authors.lastname: Calvano
authors.forename: David P
authors.initials: DP
authors.lastname: Sundin
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Lowry
mesh_terms: D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000378:metabolism; D019446:Endotoxemia / Q000188:drug therapy* / Q000378:metabolism*; D004731:Endotoxins / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005342:Fibrinolysis; D006801:Humans; D007249:Inflammation; D010919:Placebos / Q000378:metabolism; D011486:Protein C / Q000378:metabolism / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology*; D018805:Sepsis / Q000188:drug therapy; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004731:Endotoxins; D010919:Placebos; D011486:Protein C; D011994:Recombinant Proteins; D013917:Thrombin; C421124:drotrecogin alfa activated