PHARMACOLOGICAL DISPOSITION OF 1,4-BIS(2-[(2-HYDROXYETHYL)AMINO]-ETHYLAMINO)-9,10-ANTHRACENEDIONE DIACETATE IN THE DOG

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (5) , 1427-1430
Abstract
1,4-Bis{2-[(2-hydroxyethyl)amino]ethylamino}-9,10-anthracenedione (NSC 287513) (HAQ) may be selected for clinical trial based on its activity against a number of transplantable rodent tumor cell lines. Using a high-pressure liquid chromatograph assay, the pharmacological fate of HAQ in beagles was studied. After i.v. administration of HAQ at 15 mg/kg (300 mg/m2), the initial plasma t1/2 [half-time] of the agent was 9.4 min; the terminal t1/2 was 115.2 min. A maximal plasma concentration of 24.9 mg HAQ/l was attained. A high plasma clearance of 23.5 ml/kg per min was observed in these animals. The extrapolated apparent volume of distribution was 693.7 ml/kg, comparable to that of antipyrine in the dog. In 5 h, 24.0% of the administered HAQ was excreted in the urine unchanged; a trace of a metabolite was detected, amounting to less than 2% of the UV-absorbing (254 nm) materials. Hepatobiliary excretion constituted the primary route of drug elimination since 39.5% of the dose was in the bile during the same period. An extraction procedure was developed to quantify HAQ in tissue homogenates with 75-80% recovery. At autopsy, 5 h after dosing, drug distribution in terms of percentage of the dose administered is as follows: liver, 7%; kidneys, 3.5%; pancreas, 3.1%; small intestine, 1.5%; stomach, 1.3%; spleen, 0.7%; lungs, 0.5%; heart, 0.4%; large intestine, 0.4%; and brain, 0.2%.