Pharmacokinetics of recombinant transgenic antithrombin in volunteers.
Adequate levels of antithrombin (AT) III are essential for anticoagulation during cardiopulmonary bypass. Levels of AT are often decreased in patients receiving heparin before surgery. In these patients supplementation with exogenous AT can suppress the coagulation pathway and possibly decrease the risk of postoperative coagulopathy. However, the pharmacokinetics of AT have not been extensively analyzed. In this study we investigated the pharmacokinetics of transgenic recombinant AT in healthy volunteers. The concentrations of AT, after initial doses given over 30 min, were best described by a weight-normalized two-compartment model. The fast compartment volume was 41.1 mL/kg and the volume of distribution was 115.4 mL/kg. Intercompartmental clearance was 0. 0763 mL. kg(-1). min(-1) and elimination clearance was 0.0383 mL. kg(-1). min(-1). These variables are equivalent to a distribution half-life of 196 min and an elimination half-life of 2568 min. Approximately 75% of the supplemental dose is removed from plasma by the initial distribution process. A single supplemental dose of transgenic recombinant antithrombin restoring levels to 120%-150% of normal can provide adequate levels for the usual duration of cardiopulmonary bypass.


CONCLUSIONS
A single supplemental dose of transgenic recombinant antithrombin restoring levels to 120%-150% of normal can provide adequate levels for the usual duration of cardiopulmonary bypass.
Lu
W
W
Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia 30322-1104, USA.
Mant
T
T
Levy
J H
JH
Bailey
J M
JM
D000328:Adult; D000991:Antithrombins / Q000493:pharmacokinetics*; D002315:Cardiopulmonary Bypass; D006801:Humans; D008297:Male; D008954:Models, Biological; D011994:Recombinant Proteins / Q000493:pharmacokinetics
D000991:Antithrombins; D011994:Recombinant Proteins