Coagulation recovery after warfarin-induced hypoprothrombinaemia by oral administration of liposomally-associated vitamin K1 to rabbits.

Abstract

The effect of liposomally-associated vitamin K1, administered orally, was investigated using rabbits with warfarin-induced hypoprothrombinaemia, and evaluated in comparison with other dosage forms of the vitamin, including a vitamin K1 emulsion, the physical mixture of the emulsion with empty liposomes, polyoxyethylene hydrogenated castor oil (HCO-60)-stabilized emulsion and the vitamin solubilized by HCO-60. The effect on blood coagulation recovery of each preparation was estimated as the time required for the prothrombin complex activity to return to 60% (TPCA60). The coagulation recovery time of the liposomal preparation was much faster than that of the other preparations and it was compared with the response to intravenous administration in which the vitamin was considered to be 100% available. The TPCA60 for the intravenous administration was 1.9 h, that for the oral liposomal preparation was 6.2 h, HCO-60 solubilized vitamin 13.6 h, HCO-60 stabilized emulsion 19.6 h, the physical mixture 17.8 h and plain emulsion 18.2 h. The vitamin K1 dose was maintained at 12 mg kg-1 in each instance.