Elsevier

Brain Research

Volume 791, Issues 1–2, 27 April 1998, Pages 313-316
Brain Research

Short communication
Low blood–brain barrier permeability to azidothymidine (AZT), 3TC™, and thymidine in the rat

https://doi.org/10.1016/S0006-8993(98)00139-5Get rights and content

Abstract

The blood–brain barrier (BBB) permeability to [3H]-azidodeoxythymidine (AZT), deoxythiacytidine (3TC™), and thymidine was studied using both an intravenous injection/external organ (IV/EO) method and an internal carotid artery perfusion (ICAP) technique in parallel with [14C]-sucrose as a plasma volume marker. The brain volumes of distribution (VD) of the three compounds approximated that of sucrose with either method. Although the lipid solubility of AZT, as determined by the 1-octanol/buffer partition coefficient (P), was 16-fold higher than that of thymidine, the BBB permeability-surface area (PS) products were almost identical, consistent with preferential efflux of AZT from brain to blood.

Section snippets

Acknowledgements

This study was supported by BioChem Pharma.

References (20)

  • E.M. Cornford et al.

    Independent blood–brain barrier transport systems for nucleic acid precursors

    Biochim. Biophys. Acta

    (1975)
  • A.E. Ahmed et al.

    Comparative distribution and whole-body autoradiographic distribution of [2-14C]azidodeoxythymidine and [2-14C]thymidine in mice

    J. Pharmacol. Exp. Ther.

    (1991)
  • C.C.J. Carpenter et al.

    Antiretroviral therapy for HIV infection in 1997

    JAMA

    (1997)
  • K.H. Dykstra et al.

    Microdialysis study of zidovudine (AZT) transport in rat brain

    J. Pharamcol. Exp. Ther.

    (1993)
  • D.D. Ho et al.

    Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurological syndromes related to the acquired immunodeficiency syndrome

    New Engl. J. Med.

    (1985)
  • R. Masereeuw et al.

    In vitro and in vivo transport of zidovudine (AZT) across the blood–brain barrier and the effect of transport inhibitors

    Pharm. Res.

    (1994)
  • J.E. Merrill et al.

    HIV-1, macrophages, glial cells and cytokines in AIDS nervous system disease

    FASEB J.

    (1991)
  • S.Y. Pang et al.

    The structure of HIV DNA in brain and blood of AIDS patients

    Nature

    (1990)
  • W.M. Pardridge, Peptide Drug Delivery to the Brain, Raven Press, New York, 1991, pp....
  • W.M. Pardridge et al.

    Transport of steroid hormones through the rat blood–brain barrier. Primary role of albumin-bound hormone

    J. Clin. Invest.

    (1979)
There are more references available in the full text version of this article.

Cited by (0)

View full text