CHRONO-PHARMACOLOGICAL STUDY OF ONCE-DAILY CURATIVE DOSE OF A LOW-MOLECULAR-WEIGHT HEPARIN (200 IU ANTIXA KG OF DALTEPARIN) IN 10 HEALTHY-VOLUNTEERS/

Low molecular weight heparin (LMWH) is currently prescribed for the tr eatment 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 effic acy. We decided to study the chrono-pharmacology of curative dose of L MWH once daily administrated according to the one previously described with unfractionated heparin (UFH). Ten healthy volunteers participate d in an open three-period crossover study according to three 24 h cycl es, separated by a wash-out interval lasting 7 days: one control cycle without injection, two cycles with subcutaneous injection of 200 IU a ntiXa/kg of Dalteparin (Fragmin(R)) 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 (T T), prothrombin time (PT) and tissue factor pathway inhibitor (TFPI) w ere 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) ac tivity was observed. Thus the biological anticoagulant effect of 200 I U antiXa/kg of Dalteparin seems to be higher after an evening injectio n than after a morning injection. A chrono-therapeutic approach with L MWH, as prescribed once daily, deserves further investigation since ou r results suggest that a preferential injection time may optimise the clinical efficacy of these LMWH.