Vitamin K-reversible hypoprothrombinemia in rats. I. Sex differences in the development of hypoprothrombinemia and the effects of beta-lactam antibiotics.
Male and female rats were fed an ordinary diet which contained about 500 ng vitamin K/g or a vitamin K-deficient diet containing less than 5 ng vitamin K/g. Hypoprothrombinemic changes such as prolongation of the prothrombin time (PT) and activated partial thromboplastin time (APTT) were detected in male rats within 4-6 days after feeding of the vitamin K deficient diet. Blood clotting factor VII and descarboxy prothrombin (PIVKA) levels changed rapidly, with maximum alteration at 2-4 days. Similar changes in factor VII and PIVKA levels were observed in female rats, but they appeared only after feeding of the K deficient diet for a long period. PT and APTT in female rats showed slight or no alteration even after 10 day feeding of the K-deficient diet. These results indicate that male rats are more susceptible to vitamin K deficiency than female rats. Administration of latamoxef led to a dose-dependent development of hypoprothrombinemia in vitamin K-deficient female rats. The hypoprothrombinemia in vitamin K-deficient female rats was caused by beta-lactam antibiotics with N-methyltetrazolethiol, thiadiazolethiol and methyl-thiadiazolethiol as the 3'-position substituent of the cephem nucleus.
Matsuura
M
M
Kanzakigawa Laboratory, Shionogi Research Laboratories, Osaka, Japan.
Satoh
S
S
Takano
K
K
Harauchi
T
T
Yoshizaki
T
T
Kobayashi
F
F
Matsubara
T
T
Uchida
K
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D005167:Factor VII / Q000378:metabolism; D005260:Female; D007020:Hypoprothrombinemias / Q000188:drug therapy*; D008297:Male; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D014812:Vitamin K / Q000627:therapeutic use*; D014813:Vitamin K Deficiency / Q000097:blood; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D014812:Vitamin K; D005167:Factor VII