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Hydroxyurea Transport Across the Blood–brain and Blood–cerebrospinal Fluid Barriers of the Guinea-pig by M. Dogruel; J. E. Gibbs; S. A. Thomas is a Neuroscience article available to read on EtoBox.

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## Abstract Hydroxyurea is used in the treatment of HIV infection in combination with nucleoside analogues, 2′3′‐didehydro‐3′deoxythymidine (D4T), 2′3′‐dideoxyinosine or abacavir. It is distributed into human CSF and is transported from the CSF to sub‐ependymal brain sites, but its movement into the brain directly from the blood has not been studied. This study addressed this by a brain perfusion technique in anaesthetized guinea‐pigs. The carotid arteries were perfused with an artificial plasma containing [^14^C]hydroxyurea (1.6 μm) and a vascular marker, [^3^H]mannitol (4.6 nm). Brain uptake of [^14^C]hydroxyurea (8.0 ± 0.9%) was greater than [^3^H]mannitol (2.4 ± 0.2%; 20‐min perfusion, __n__ = 8). CSF uptake of [^14^C]hydroxyurea (5.6 ± 1.5%) was also greater than [^3^H]mannitol (0.9 ± 0.3%; __n__ = 4). Brain uptake of [^14^C]hydroxyurea was increased by 200 μm hydroxyurea, 90 μm D4T, 350 μm probenecid, 25 μm digoxin, but not by 120 μm hydroxyurea, 16.5–50 μm D4T, 90 μm 2′3′‐dideoxyinosine or 90 μm abacavir. [^14^C]Hydroxyurea distribution to the CSF, choroid plexus and pituitary gland remained unaffected by all these drugs. The metabolic half‐life of hydroxyurea was > 15 h in

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Author

M. Dogruel; J. E. Gibbs; S. A. Thomas

Publisher

John Wiley and Sons; Wiley (Blackwell Publishing); Blackwell Publishing Inc.; Wiley (ISSN 0022-3042)

Published

2003

Language

EN

Field

Neuroscience (Life Sciences)