This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lu, K. Articles by Loo, T. L. Search for Related Content PubMed PubMed Citation Articles by Lu, K. Articles by Loo, T. L.

Pharmacological Disposition of 1,4-Bis{2-{(2-hydroxyethy)amino]ethylamino}-9,10-anthracenedione Diacetate in the Dog¹

Department of Developmental Therapeutics, The University of Texas System Cancer Center M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030

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 tumors. Using a high-pressure liquid chromatograph assay, we have studied the pharmacological fate of HAQ in beagles. After i.v. administration of HAQ at 15 mg/kg (300 mg/sq m), the initial plasma t_1/2 of the agent was 9.4 min, and the terminal t_1/2 was 115.2 min. A maximal plasma concentration of 24.9 mg of HAQ per liter was attained. A high plasma clearance of 23.5 ml/kg/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 hr, 24.0% of the administered HAQ has been excreted in the urine unchanged, and a trace of a metabolite was detected, amounting to less than 2% of the UV-absorbing (254 nm) materials. However, hepatobiliary excretion constituted the primary route of drug elimination since 39.5% of the dose was found in the bile during the same period. An extraction procedure has been developed to quantify HAQ in tissue homogenates with 75 to 80% recovery. At autopsy, 5 hr 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%.

¹ Supported by National Cancer Institute Contract N01-CM-87185.

² To whom requests for reprints should be addressed.

Received 9/21/79. Accepted 1/25/80.