title: Penetration of the blood-brain barrier by the antiviral drug (E)-5-(2-iodovinyl)-2'-deoxyuridine in a rat model of herpes encephalitis.
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.
authors.affiliation: Department of Medical Microbiology, University of Manchester, UK.
authors.forename: P E
authors.initials: PE
authors.lastname: Klapper
authors.forename: G M
authors.initials: GM
authors.lastname: Cleator
authors.forename: J M
authors.initials: JM
authors.lastname: Bruce
authors.forename: M
authors.initials: M
authors.lastname: Longson
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001345:Autoradiography; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000000981:diagnostic imaging; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002855:Chromatography, Thin Layer; D004660:Encephalitis / Q000378:metabolism*; D006561:Herpes Simplex / Q000378:metabolism*; D007065:Idoxuridine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D007457:Iodine Radioisotopes; D011877:Radionuclide Imaging; D051381:Rats; D018139:Simplexvirus
chemical_list: D000998:Antiviral Agents; D007457:Iodine Radioisotopes; C030360:5-(2-iodovinyl)-2'-deoxyuridine; D007065:Idoxuridine