Open AccessVitamin K-reversible hypoprothrombinemia in rats. I. Sex differences in the development of hypoprothrombinemia and the effects of beta-lactam antibiotics.
Author(s) -
Minoru Matsuura,
Seiji Satoh,
Kyoji Takano,
Toshio Harauchi,
Toshio Yoshizaki,
Fuminori Kobayashi,
Takashi Matsubara,
Keiji Uchida
Publication year - 1988
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.46.303
Subject(s) - hypoprothrombinemia , latamoxef , medicine , vitamin k deficiency , endocrinology , prothrombin time , vitamin , partial thromboplastin time , cefotiam , factor vii , chemistry , antibiotics , vitamin k , coagulation , biochemistry , cephalosporin
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.