Pharmacokinetic studies of standard heparin and low molecular weight heparin in patients with chronic renal failure.
The disappearance of the anticoagulant activities of a standard commercial heparin and of a low molecular weight (LMW) heparin (PK 10169), administered as single intravenous injections, was studied in patients with chronic renal failure. Heparin and LMW heparin anticoagulant activities were determined by activated partial thromboplastin time (APTT) and chromogenic assays of anti-Xa and anti-IIa activities. Following heparin injection, a fast initial decay of anticoagulant activities preceded a slow convex disappearance curve, in semilogarithmic plots. These experimental data are in agreement with a model based on a predominant saturable mechanism of elimination of heparin in patients with renal failure. The disappearance of LMW heparin anti-Xa activity was obviously different, with linear or concave elimination curves, and longer apparent half-life. Taken together, our kinetic data and those previously reported in normal subjects strongly suggest that the mechanism of elimination of the LMW heparin studied is not saturable (at least for the tested dosages), and that the kidneys play a minimal role in the elimination.
Follea
G
G
Laville
M
M
Pozet
N
N
Dechavanne
M
M
D000293:Adolescent; D000328:Adult; D005170:Factor X / Q000037:antagonists & inhibitors; D015951:Factor Xa; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D007700:Kinetics; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008970:Molecular Weight; D010314:Partial Thromboplastin Time; D010978:Platelet Factor 4 / Q000378:metabolism; D011516:Prothrombin / Q000037:antagonists & inhibitors
D010978:Platelet Factor 4; D011516:Prothrombin; D005170:Factor X; C025337:Factor IIa; D006493:Heparin; D015951:Factor Xa