The pharmacologic fate of 2,5-diaziridinyl-3,6-bis(carboethoxyamino) 1,4-benzoquinone (AZQ NSC-182986) by intracarotid or intravenous administration in beagles

Lynn G. Feun, Niramol Savaraj, Katherine Lu, Zhengang Guo, L. Gilbert Raulston, Robert S. Benjamin, William S. Fields, Ti Li Loo

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Beagle dogs received either intravenous (I.V.) or intracarotid (I.C.) 14C ring labelled 2,5-diaziridinyl-3,6-bis-(carboethoxyamino) 1,4-benzoquinone (AZQ) at a dose of 2 mg/ kg. Blood, urine and cerebrospinal fluid (CSF) samples were collected at intervals. At varying times, dogs from each group were sacrificed and histologic examination and drug determinations were performed on the major organs. By both routes of administration, the elimination of AZQ from plasma was biphasic with an initial half-life of 18 min and a terminal half-life of 26 hr. The apparent volume of distribution was 7.9 1/ kg and the total clearance was 3.5 ml/kg/h. The 96 hr cumulative urinary excretion of total 14C was 41% of the administered dose, including 4% as the unchanged drug. At 1, 48, and 96 hr after I. C. AZQ, drug concentrations in the brain tissue were twice those by the 1.V. route. High drug concentrations in the CSF were produced by both routes, although the CSF to plasma ratio was higher by I.C. than LV. In extracranial organs, tissue concentrations of AZQ were at least twice as high by LV. than by I.C. administration. No significant clinical or neurologic toxicity were noted when AZQ was given I.C. In the dog I.C. administration of AZQ seems to accelerate drug entry into the brain tissue.

Original languageEnglish (US)
Pages (from-to)219-224
Number of pages6
JournalJournal of neuro-oncology
Volume1
Issue number3
DOIs
StatePublished - Sep 1 1983
Externally publishedYes

Keywords

  • AZQ
  • brain
  • dogs
  • intracarotid
  • pharmacology

ASJC Scopus subject areas

  • Neuroscience(all)
  • Oncology
  • Clinical Neurology
  • Cancer Research

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