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...

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Bibliographic Details
Published in:Japanese journal of pharmacology 1988, Vol.46 (3), p.303-310
Main Authors: MATSUURA, Minoru, SATOH, Seiji, TAKANO, Kyoji, HARAUCHI, Toshio, YOSHIZAKI, Toshio, KOBAYASHI, Fumihiko, MATSUBARA, Takashi, UCHIDA, Kiyohisa
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - pharmacology
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
beta-Lactams
Biological and medical sciences
Blood Coagulation - drug effects
Factor VII - metabolism
Female
Hypoprothrombinemias - drug therapy
Male
Medical sciences
Partial Thromboplastin Time
Pharmacology. Drug treatments
Prothrombin Time
Rats
Rats, Inbred Strains
Sex Factors
Vitamin K - therapeutic use
Vitamin K Deficiency - blood
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Summary: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.
ISSN:0021-5198
1347-3506
DOI:10.1016/S0021-5198(19)43316-7