The pharmacokinetics and pharmacodynamics of dermatan sulphate MF701 during haemodialysis for chronic renal failure.
Single i.v. bolus doses of dermatan sulphate MF701 were administered before the onset of haemodialysis to patients with chronic renal failure, to prevent clotting in the extracorporeal circuit. Six patients received 2 mg kg-1; six were given 2.5 and 3 mg kg-1; 13 received 4.5 and 6 mg kg-1. Plasma MF701 concentrations (chromogenic assay), activated partial thromboplastin time (APTT) and plasma markers of coagulation and platelet activation (TAT and beta-TG) were measured over 4 or 8 h from the onset of dialysis. The disposition of MF701 was described by a monoexponential function. C(0) and AUC values increased proportionally with dose. Volumes of distribution (approximately 4 l) were dose-independent. Half-lives showed a non significant increase with dose (from 2.2 to 3.1 h) and were 2.5-3 times longer than those reported for healthy subjects. There was a significant correlation between plasma MF701 concentration and its effects in prolonging APTT and suppressing TAT and beta-TG generation during dialysis.
Gianese
F
F
Medical Department, Mediolanum Farmaceutici, Milan, Italy.
Nurmohamed
M T
MT
Imbimbo
B P
BP
Büller
H R
HR
Berckmans
R J
RJ
Ten Cate
J W
JW
D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects; D003871:Dermatan Sulfate / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D006435:Renal Dialysis
D003871:Dermatan Sulfate