Elsevier

Life Sciences

Volume 47, Issue 9, 1990, Pages 781-788
Life Sciences

Brain and cerebrospinal fluid uptake of zidovudine (AZT) in rats after intravenous injection

https://doi.org/10.1016/0024-3205(90)90550-BGet rights and content

Abstract

Uptake kinetics of zidovudine into cerebrospinal fluid (CSF) and brain tissue were determined in adult Sprague Dawley male rats after single intravenous injection of 6.7 mg/kg (25 μmol/kg). The drug kinetics in plasma followed biexponential disposition with an initial distribution half-life of approximately 11 minutes and an elimination half-life of 40 minutes. Over the plasma concentration range of 0.2 to 10 μg/ml, the cerebrospinal fluid to plasma ratio averaged 14.8±1.9% whereas the mean brain tissue to plasma ratio was 8.2±1.2% (uncorrected) or 2.3±1.8% (corrected) for the brain vascular space contribution. Simultaneous nonlinear regression analysis of brain, CSF and plasma concentration data indicate that the overall rate constant for efflux of drug from brain is ∼75-fold higher and from CSF is 8-fold higher than the respective rate constants for influx. Thus, the ratio of the efflux to influx appears to be the predominant factor in determining the net accumulation of drug into CSF and brain parenchymal tissue.

References (20)

  • R. Yarchoan et al.

    Lancet

    (1987)
  • M.A. Hedaya et al.

    J. Pharm. Sci.

    (1989)
  • E. Preston et al.

    J. Neurosci. Methods

    (1983)
  • R.W. Price et al.

    Science

    (1988)
  • K. Kieburtz et al.

    Neurologic Clinics

    (1989)
  • A.M. Allworth et al.

    Med. J. Aust.

    (1989)
  • J. Matthes et al.

    Arch. Dis. Child.

    (1988)
  • A. Brunetti et al.

    J. Nucl. Med.

    (1989)
  • R.W. Klecker et al.

    Clin. Pharmacol. Ther.

    (1987)
  • T. Terasaki et al.

    J. Infect. Dis.

    (1988)
There are more references available in the full text version of this article.

Cited by (0)

View full text