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  • Title: Vitamin K-reversible hypoprothrombinemia in rats. I. Sex differences in the development of hypoprothrombinemia and the effects of beta-lactam antibiotics.
    Author: Matsuura M, Satoh S, Takano K, Harauchi T, Yoshizaki T, Kobayashi F, Matsubara T, Uchida K.
    Journal: Jpn J Pharmacol; 1988 Mar; 46(3):303-10. PubMed ID: 3379837.
    Abstract:
    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.
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