An evaluation of the biological response to Fraxiparine, (a low molecular weight heparin) in the healthy individual.
The tolerance of a low molecular weight heparin (Fraxiparine, Choay, Paris, France) in normal individuals was determined using a two part investigation. Study 1 consisted of administering escalating doses of Fraxiparine in a single blinded, placebo controlled, rising dose tolerance evaluation. The daily doses tested were 3750 U AXA IC, 7500 U AXa IC, 11250 U AXa IC, 15000 U AXa IC, and 22500 U AXa IC Fraxiparine subcutaneously for 5 consecutive days. In study 2, we compared the tolerance of unfractionated heparin (UH) administered as 5000 IU every 8 hours, to that of 7500 U AXa IC/day or 15000 U AXa IC/day of Fraxiparine administered once daily. Our results indicated very good tolerance to this low molecular weight heparin (LMWH) at doses up to and including 22500 U AXa IC/day. We observed significantly elevated increases in transaminases following LMWH administration. In our second study we observed that the increase in serum transaminases seen after 15000 U AXa IC/day Fraxiparine was without significant difference from that observed following UH (5000 IU every 8 hours). AXa examination revealed an accumulation of AXa effect after 5 days of administration at doses greater than 15000 U AXa IC, and there was good correlation between AXa and APTT at Fraxiparine doses greater than 15000 U AXa IC/day. No thrombocytopenia was associated with Fraxiparine. We conclude that Fraxiparine is relatively well tolerated and shows accumulation after daily dosing with greater than 15000 U AXa IC.
Freedman
M D
MD
Sanofi Research, New York, New York.
Leese
P
P
Prasad
R
R
Hayden
D
D
D000328:Adult; D004311:Double-Blind Method; D006207:Half-Life; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D011897:Random Allocation; D016037:Single-Blind Method; D013997:Time Factors; D000637:Transaminases / Q000097:blood*
D006495:Heparin, Low-Molecular-Weight; D000637:Transaminases