436 VITAMIN K GROUP 



analogs become inconsequential. Little has been done to investigate the 

 possibility of using smaller quantities of vitamin K, but from a practical 

 point of view there would seem to be little advantage. 



Richards and Shapiro^ stress that larger doses of vitamin K are needed 

 for the treatment of overdicoumarolization, in the presence of hepatic 

 damage, or simply in the performance of an evaluation of hepatic function. 

 Cromer and Barker, among others,^ found that 60 mg. of anhydrous 

 menadione bisulfite (equivalent to 72 mg. of the hydrated ester) was 

 sufficient to correct the prolonged "prothrombin time" of most patients 

 who had responded to dicoumarol with unusual vigor. However, an occa- 

 sional dicoumarolized patient is unresponsive to the water-soluble analogs 

 even in doses of 600 mg. given intravenously. In such cases the administra- 

 tion of phytyl menadione (up to 1 g. orally or intravenously) has been re- 

 markably successful.'^ The more stable oxide of phytyl menadione may 

 prove to be practical. 



C. MODE OF ADMINISTRATION 



The water-soluble naphthoquinones may be given orally, subcutaneously, 

 intramuscularly, intraperitoneally, or intravenously with substantially the 

 same results; regardless of the route a lag of 1 to 2 hours occurs before any 

 clotting response is perceptible.^ Inunctions of water-soluble vitamin K 

 derivatives have proved effective,^ but they may be irritating.^" The fat- 

 soluble K-quinones are generally given orally, accompanied by bile salts in 

 the case of obstructive jaundice or biliary fistula but not in antidicoumarol 

 therapy where bile is available to the bowel. Davidson and MacDonald^ 

 have described the suspension of fat-soluble preparations for intravenous 

 use: up to 450 mg. of vitamin Ki was dissolved in 15 to 20 ml. of absolute 



« R. K. Richards and S. Shapiro, /. Pharmacol. Exptl. Therap. 84, 93 (1945). 



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 Barker, Proc. Staff Meetings Mayo Clinic 19, 217 (1944). 



7 C. S. Davidson and H. MacDonald, New Engl. J. Med. 229, 353 (1943) ; S. P. Lucia 

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8 H. C. Willumsen, H. E. Stadler, and C. A. Owen, Proc. Soc. Exptl. Biol. Med. 47, 

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