Penetration of the blood-brain barrier by the antiviral drug (E)-5-(2-iodovinyl)-2'-deoxyuridine in a rat model of herpes encephalitis

P E Klapper, G M Cleator, J M Bruce, M Longson

Research output: Contribution to journalArticlepeer-review

Abstract

The blood-brain barrier penetration of a radiohalogenated (125I) derivative of the antiviral drug (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU) was investigated in a rat model of herpes encephalitis. CNS delivery was assessed by external gamma camera scintigraphic imaging in vivo, a technique which may have general application in evaluating brain specific delivery of drugs, and by autoradiography of cryostat sections of rat brain. Radiohalogenated IVDU was found to be almost totally excluded from the CNS. These findings may be explained in terms of the poor lipid solubility of IVDU (in vitro oil/aqueous salt solution partition coefficient 0.012). Since IVDU appears in CSF after carotid artery administration, our results stress the necessity, in the design of compounds for the treatment of CNS infections, of distinguishing blood-brain, blood-CSF, and CSF-brain drug barriers. The significance of our data both in relation to the development of neuro-radiological diagnosis and antiviral chemotherapy of CNS infection is discussed.

Original languageEnglish
Pages (from-to)57-67
Number of pages11
JournalDrug design and delivery
Volume3
Issue number1
Publication statusPublished - 1 Jul 1988

Keywords

  • Animals
  • Antiviral Agents/pharmacokinetics
  • Autoradiography
  • Blood-Brain Barrier/drug effects
  • Brain/diagnostic imaging
  • Chemical Phenomena
  • Chemistry, Physical
  • Chromatography, Thin Layer
  • Encephalitis/metabolism
  • Herpes Simplex/metabolism
  • Idoxuridine/analogs & derivatives
  • Iodine Radioisotopes
  • Radionuclide Imaging
  • Rats
  • Simplexvirus

Fingerprint

Dive into the research topics of 'Penetration of the blood-brain barrier by the antiviral drug (E)-5-(2-iodovinyl)-2'-deoxyuridine in a rat model of herpes encephalitis'. Together they form a unique fingerprint.

Cite this