Pharmacodynamic study of low molecular weight dermatan sulphate (Desmin) after a single subcutaneous administration in patients with renal insufficiency.
The pharmacodynamic pattern of low molecular weight dermatan sulphate (CAS 24967-94-0, Desmin-LMWDS) was studied in patients presenting chronic renal insufficiency. Three groups of six patients were defined according to their creatinine clearance: group 1, more than 50 ml/min, group 2 between 10 and 50 ml/min and group 3 lower than 10 ml/min (haemodialized patients). Desmin-LMWDS concentrations were determined with the Heptest assay and the chromogenic specific heparin cofactor II dependent anti IIa assay. In patients of group 1 affected by moderate renal insufficiency, the pharmacodynamic profiles were roughly comparable to those obtained in normal subjects. In the two other groups, the profiles were markedly modified by the renal insufficiency. The maximal concentrations were doubled and the areas under the time-activity curve were 4-fold higher in haemodialyzed (group 3) and severe renal insufficient patients (group 2) than in patients of group 1. The clearance of the anti IIa activity were 13.98 +/- 6.25 l/h; 4.12 +/- 2.64 l/h and 2.94 +/- 1.53 l/h and the half-lives were 2.79 +/- 2.60 h, 6.15 +/- 4.02 h and 11.51 +/- 6.54 h in groups 1 to 3, respectively (p < 0.05). The Desmin-LMWDS clearance was directly correlated to the creatinine clearance (r = 0.8244, n = 18, p < 0.001). Thus, as for low molecular weight heparin, renal function plays a major role in the elimination of low molecular weight dermatan sulphate.
Saivin
S
S
Laboratoire de Pharmacocinétique et Toxicologie Clinique, Hôpital Rangueil, Toulouse, France.
Boneu
B
B
Ducret
F
F
Pourrat
J
J
Palazzini
E
E
Zamboni
W
W
Duchêne
P
P
Houin
G
G
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D003871:Dermatan Sulfate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015951:Factor Xa / Q000378:metabolism; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011516:Prothrombin / Q000378:metabolism; D013918:Thrombin Time
D003871:Dermatan Sulfate; D011516:Prothrombin; D015951:Factor Xa