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  • Title: Pharmacokinetic and metabolism studies of two novel 1-deaza-7,8-dihydropteridines in mice.
    Author: Noker PE, Hill DL, Kalin JR, Temple CG, Montgomery JA.
    Journal: Drug Metab Dispos; 1985; 13(6):677-81. PubMed ID: 2867870.
    Abstract:
    The disposition of two 1-deaza-7,8-dihydropteridines, NSC 269416 and NSC 350386, was studied in mice dosed iv. After dosing with 25 mg/kg of NSC 269416, serum levels fell in two phases with half-lives of 3.1 and 32 min. Highest levels were in liver, kidney, spleen, lungs, and small intestines; little compound was detected in brain, muscle, or fat. Although no metabolites were detected in serum or tissues, four metabolites, but no parent compound, were present in urine. After administration of 7 mg/kg of NSC 350386, serum levels fell with apparent half-lives of 4.3 (alpha-phase) and 49 min (beta-phase). At most times of analysis, liver, kidney, spleen, lung, brain, fat, and small intestines had similar concentrations of the compound. In 24 hr, less than 5% of the dose was excreted into urine unchanged. Analyses of collected urinary products indicated that, in vivo, NSC 350386 was metabolically hydroxylated and conjugated with glucuronic acid and also cleaved, a process involving removal of the ethoxycarbonyl group.
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