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THE ACUTE TOXICITY OF BIMIDA, A PROSPECTIVE HEPATOBILIARY SCANNING AGENT
Author(s) -
Keayes Gabrielle C,
Gallagher Clifford H
Publication year - 1984
Publication title -
australian journal of experimental biology and medical science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0004-945X
DOI - 10.1038/icb.1984.62
Subject(s) - toxicity , acute toxicity , alkaline phosphatase , in vivo , in vitro , microsome , chemistry , pharmacology , enzyme , medicine , endocrinology , biochemistry , biology , microbiology and biotechnology
Summary The acute toxic effects of dimethyl benzimidazolyl methyliminodiacetic acid (Bimida), a prospective hepatobiliary scanning agent when labelled with 99m Tc, are described. The LD 50 in male and female rats was 150 mg/kg, and in mice 100 mg/kg, males, and 75 mg/kg, females, up to 2000 times the diagnostic dose required in patients. Clinical signs associated with administration of lethal and sublethal doses of Bimida suggested the cause of death to be an acute hypocalcaemic episode; this was confirmed. in vivo and in vitro . A significant reduction in alkaline phosphatase (ALP) activity and Ca 2+ concentration associated with administration of 100 human equivalent doses (HED) Bimida and 99m Tc labelled Bimida was measured in serum and microsomal preparations of liver and intestine. An in vitro system indicated that this response was prevented in the presence of adequate Ca 2+ , suggesting that ALP activity is depressed because chelation of the metal ion by Bimida causes a shortage of the Ca 2+ needed to activate the enzyme.