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Pharmacokinetics and Clinical Use of Drotrecogin alfa (activated) in Patients with Severe Sepsis
Author(s) -
Olsen Keith M.,
Martin Steven J.
Publication year - 2002
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.22.18.196s.33708
Subject(s) - drotrecogin alfa , medicine , dosing , fibrinolysis , sepsis , pharmacokinetics , intensive care medicine , adverse effect , placebo , clinical trial , pharmacodynamics , pharmacology , severe sepsis , septic shock , alternative medicine , pathology
Drotrecogin alfa (activated) pharmacokinetics have been reported in healthy volunteers and in patients with severe sepsis. Clearance is rapid and appears to increase with weight; consequently, drotrecogin alfa (activated) is dosed on a weight basis. Drotrecogin alfa (activated) promotes fibrinolysis and inhibits thrombin production to produce an anticoagulant effect. The primary adverse events are related to its pharmacologic activity, with serious bleeding reported in 3.5% of patients receiving the drug in a multicenter phase III trial compared with 2.0% for patients receiving placebo. Monitoring parameters correspond with bleeding and should include international normalized ratio, platelet count, hematocrit, and overt signs of bleeding. Because of the protein nature of drotrecogin alfa (activated), pharmacists should be aware of the proper preparation and stability issues in order to afford efficient, cost‐effective administration. As further data on drotrecogin alfa (activated) therapy become available, dosing and monitoring strategies may be altered to optimize the clinical benefits.