Efficacy of Water-Soluble Derivatives of Vitamin K₁ in Counteracting Drug-Induced Hypoprothrombinemia

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.