Pharmacokinetics of 2′-deoxycoformycin, an inhibitor of adenosine deaminase, in the rat

J. D. Geiger, J. L. Lewis, C. J. MacIntyre, J. I. Nagy

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The distribution of the potent inhibitor of adenosine deaminase (ADA), 2′-deoxycoformycin (DCF), in the brain of the rat and its inhibition of ADA in brain and gut was determined. The accumulation of [3H]DCF in brain was maximal 2 hr after intraperitoneal injection and elimination was best described by a two compartment model having t 1 2 phases of about 1-5 hr and 50 hr. The activity of ADA in gut exhibited dose-related inhibition at 1.9, 3.7 and 18.6 μmol/kg (i.p.) and returned to normal by 16 days. In brain, ADA was inhibited by about 95% at all three of these doses of DCF 2hr after injection and activity returned to control levels by 30 days with the two smaller doses, but remained at 66% of control levels at 50 days with 18.6 μmol/kg. The t 1 2 of the recovery of the activity of ADA in both brain and gut was found to be dose-dependent. The failure of the activity of ADA in brain to recover after treatment with 18.6 μmol/kg suggests either long-term down-regulation of the expression of ADA or irreversible damage to ADA-containing neurons.

Original languageEnglish (US)
Pages (from-to)1383-1387
Number of pages5
JournalNeuropharmacology
Volume26
Issue number9
DOIs
StatePublished - Sep 1987

Keywords

  • 2'-deoxycoformycin
  • adenosine deaminase
  • pharmacokinetics
  • rat brain

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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