The relative efficacies of vitamin K1 emulsion and several water-soluble derivatives of vitamin K1 were determined in dogs rendered hypoprothrombinemic by Dicumarol and Dipaxin.

In short term experiments equimolar intravenous doses of the disodium salt of 2-methyl-3-phytyl-1,4-naphthohydroquinone-1,4-diphosphate and of vitamin K1 emulsion exhibited like activity in reversing Dicumarol- and Dipaxin-induced hypoprothrombinemia. By this route, the 4-monophosphate derivative showed comparable activity to the 1,4-diphosphate, but the 1-propionate-4-phosphate derivative was less potent.

At equimolar dosage levels, the water-soluble diphosphate derivative was found to possess oral activity equivalent to that of vitamin K1 emulsion. It was appreciably more effective than the emulsion, however, by the intramuscular route.

With both K1 emulsion and the water-soluble diphosphate derivative, the most rapid effect followed intravenous administration. Oral treatment was less rapid and intramuscular the slowest.

Data obtained in prophylactic and therapeutic studies indicate that water-soluble vitamin K1 has a shorter duration of action than vitamin K1 emulsion. Because of this property, it should be possible to control treatment more precisely with water-soluble vitamin K1 and also to effect a rapid reversal of excessive hypoprothrombinemia with less liability of including refractoriness to reinstitution of anticoagulant therapy.

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