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The pharmacologic fate of the antitumor agent 2-amino-1,3,4-thiadiazole in the dog.

Abstract：

:Anticipating the renewed clinical trial of the antitumor agent 2-amino-1,3,4-thiadiazole (AT, NSC-4728), we have studied the pharmacologic fate of AT-5-14C in beagle dogs. The drug was only minimally metabolized in 5 h; the radioactivities in the urine, and particularly in the plasma, resided almost entirely in unchanged AT. In four dogs, after IV administration of AT-5-14C at 10 mg/kg (200 mg/m2), 150-200 muCi per animal, the terminal plasma t1/2 of AT was 13 h, and less than 10% of the administered dose appeared in the urine in 5 h. When the dose was raised to 25 mg/kg (500 mg/m2) in four dogs, the average plasma t1/2 of AT was 10 h; the 5-h cumulative excretion of the agent was 9% of the dose in the urine, 0.3% in the bile, and 0.1% as 14CO2 in the expired air. The average total clearance of AT was 0.70 ml/kg/min. Drug concentrations in the cerebrospinal fluid were 95% of those in the plasma at semi-steady state. At autopsy 5 h after dosing, more than 75% of the administered radioactivity was retained in the body, the highest amounts in terms of micrograms per gram of wet tissue being in the liver, kidney, lung and stomach. No appreciable changes in AT pharmacokinetics were evident upon simultaneous IV administration of allopurinol at 30 or 60 mg/kg. AT was less than 7% bound to dog plasma protein at 25 degrees C in concentrations of 12-100 microgram/ml.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

Lu K,Loo TL

doi

10.1007/BF00255274

subject

Has Abstract

pub_date

1980-01-01 00:00:00

pages

275-9

issue

4

eissn

0344-5704

issn

1432-0843

journal_volume

4

pub_type

杂志文章

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