Abstract
The absorption, distribution, excretion and biotransformation of carbazilquinone [2, 5-bis(1-aziridinyl)-3-(2-carbamoyloxy-1-methoxyethyl)-6-methyl-1, 4-benzoquinone], a new antitumor agent, in mice were investigated after oral and intravenous administration of the drug labeled with 14C at the aziridinyl moiety. After intravenous and oral administration, about 50% of the dose was recovered in the urine during the first 24 hr, and about 25% and 40% in the feces, respectively. A high absorptivity of the drug from the intestine and a high participation of biliary excretion were demonstrated by in situ experiments with ligated loop of a rat small intestine and with rats cannulated at the bile duct, respectively. Whole-body autoradiography and radioassay revealed that a very high uptake of radioactivity occurs mainly in the excretory organs such as the liver, gall bladder, intestine, kidney, and urinary bladder, and a high uptake in the lung, salivary gland, and hypophysis. An appreciable uptake of radioactivity was also observed in the adrenal medulla, spleen, thymus, and bone marrow, wherein the concentration appears to increase gradually up to 3 hr after administration and retained for more than 24 hr. Carbazilquinone was found to be excreted in the urine as more than 15 kinds of metabolites, most of which are non-extractable with ethyl acetate and are thus polar metabolites. Two metabolites were identified as unchanged carbazilquinone and a compound in which one of the two aziridine rings is opened to form hydroxyethylamino group. After intravenous administration, the blood level of carbazilquinone declined rapidly with an approximate half-life of 13.5 min.
