HYPERVITAMINOSIS K 777 



amounts of some vitamin K-active compounds are given. Although the 

 usual daily dosages of vitamin K were formerly in the range of a few milli- 

 grams, since the advent of dicumarol several hundred milligrams of vita- 

 min Ki may be given in a single dose, without deleterious effects, to over- 

 come the anticoagulant action of dicumarol. In the tests of Phelps and 

 Jones, 2'^ some nausea was observed after the intravenous administration 

 of 150 mg. of Synkavit, while more severe reactions occurred in several 

 cases in which the dose was increased to 600 mg. On the other hand, 

 1000 mg. of phytyl menadione (vitamin Ki) caused no symptoms, although 

 a febrile response was noted when vitamin Ki oxide was employed. Stag- 

 j^gipssa obtained rapid reversal of the hypoprothrombinemia induced by 

 dicumarol, by the intravenous administration of as little as 100 mg. of 

 emulsified \'itamin Ki. KoUer et al.-^'"^ found 500 mg. of vitamin Ki 

 effective. 



Minimal lethal doses of menadione derivatives, for mice, have been 

 shown to range from 200 and 800 mg./kg. body weight for subcutaneous or 

 intramuscular administration, and from 250 to 450 mg./kg. body weight 

 when the intravenous route was employed. The average LDbo values for 

 oral administration (in mg./kg. body weight) are as follows i^^" phthiocol, 

 200;236 menadione, 500, --^fi 620,^37 SOOj^^s menadiol disuccinate, 400;239 

 and menadiol, 300,-^^ 400.-^^ For intramuscular or subcutaneous adminis- 

 tration, the values were as follows: menadione, 138"^ and 250;^^^ menadiol 

 disuccinate, 300;^^^ and menadiol, 80'^^ and 100.^^^ The figures for in- 

 travenous dosing were recorded as follows: menadione bisulfite, 250;^^" 

 menadiol disuccinate, 275;^^^ and menadiol, 450.-"*^ 



The data on the LD50 of animals other than the mouse are limited. A 

 figure of 840 mg./kg. body weight has been recorded for the chick for 

 menadione given orally. --^^ In the case of the dog, LD50 figures of 100 to 

 150-^*' and 100-^^ were given for menadione bisulfite and menadiol di- 

 succinate, respectively. The rabbit appears to be quite sensitive to 

 menadione; an LD50 of 15 to 20 mg./kg. body weight was noted when the 

 compound was given intravenously,-^^ although values as high as 100 and 

 120 mg. haA'e been recorded for the intravenous route,-'"' and 250 mg. 



235 E. T. Phelps and S. N. Jones, Bull. Georgetown Univ. Med. Center, 4, 41-44 (1950). 

 235a R. Stagnell, Am. Heart J., U, 124-130 (1952). 



235b F. Roller, A. Loeliger, and P. Fliickinger, Helv. Med. Acta, 19, 411-416 (1952). 

 23« H. Molitor and H. J. Robinson, Proc. Soc. Exptl. Biol. Med., 43, 125-128 (1940). 

 ^^ S. Ansbacher, W. C. Corwin, and B. G. H. Thomas, J. Pharmacol. Exptl. Therap., 

 75,111-124(1942). 



238 M. B. Shimkin, /. Pharmacol. Exptl. Therap., 71, 210-214 (1941). 



239 K. Fromherz, Z. Vitaminforsch., 11, 65-75 (1941). 



2« R. K. Richards and S. Shapiro, /. Pharmacol. Exptl. Therap., 84, 93-104 (1945). 



