Hypoprothrombinemic changes in blood coagulation parameters, such as prolongation of prothrombin time, increase in the level of
plasma protein induced by
vitamin K absence, and decrease in plasma
prothrombin level, were detected in rats fed a
vitamin K-deficient diet. These changes were enhanced by the administration of
beta-lactam antibiotics containing
N-methyltetrazolethiol, thiadiazolethiol or methyl-thiadiazolethiol. Microsomal
vitamin K epoxide reductase activity was suppressed with the maximum effect at 1-2 days after the treatment and with recovery, thereafter, gradually to the normal level after 5-7 days. Hypoprothrombinemic alterations in blood coagulation parameters following a single administration of
antibiotic to
vitamin K-deficient rats were somewhat delayed compared with the change in the
epoxide reductase activity, but the effects of the
antibiotic on both blood coagulation parameters and the
enzyme activity disappeared completely 7 days after the
antibiotic treatment.
Antibiotic-induced depression of the
epoxide reductase activity was observed even in the
vitamin K sufficient rats, although the hypoprothrombinemic changes in the blood coagulation parameters did not develop.
Vitamin K administration could normalize the blood coagulation parameters in the hypoprothrombinemic rats caused by treatment with the
antibiotics but without recovery of the decreased
epoxide reductase activity. These results suggest that some
antibiotics inhibit liver microsomal
vitamin K epoxide reductase, which causes
hypoprothrombinemia to develop under
vitamin K-deficient conditions.