Summary
Low molecular weight heparin (LMWH) is currently prescribed for the treatment of deep
vein thrombosis at the dose of 100 IU antiXa/kg twice daily or at a dose of 175 IU
antiXa/kg once daily with a similar efficacy. We decided to study the chrono-pharmacology
of curative dose of LMWH once daily administrated according to the one previously
described with unfractionated heparin (UFH).
Ten healthy volunteers participated in an open three-period crossover study according
to three 24 h cycles, separated by a wash-out interval lasting 7 days: one control
cycle without injection, two cycles with subcutaneous injection of 200 IU antiXa/kg
of Dalteparin (Fragmin®) at 8 a.m. or at 8 p.m. Parameters of heparin activity were analysed as maximal values
and area under the curve.
Activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time
(PT) and tissue factor pathway inhibitor (TFPI) were higher after 8 p.m. injection
than after 8 a.m. injection (p <0.05) while no chrono-pharmacological variation of
anti factor Xa (AXa) activity was observed. Thus the biological anticoagulant effect
of 200 IU antiXa/kg of Dalteparin seems to be higher after an evening injection than
after a morning injection.
A chrono-therapeutic approach with LMWH, as prescribed once daily, deserves further
investigation since our results suggest that a preferential injection time may optimise
the clinical efficacy of these LMWH.
