التفاصيل البيبلوغرافية
| العنوان: |
Hydroxyurea transport across the blood–brain and blood–cerebrospinal fluid barriers of the guinea-pig. |
| المؤلفون: |
Dogruel, M., Gibbs, J. B., Thomas, S. A. |
| المصدر: |
Journal of Neurochemistry; 10/1/2003, Vol. 87 Issue 1, p76, 9p |
| مصطلحات موضوعية: |
HIV infections, THERAPEUTICS, CEREBROSPINAL fluid, GLYCOPROTEINS, CEREBRAL ventricles |
| مستخلص: |
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 [[sup 14]C]hydroxyurea (1.6 μm) and a vascular marker, [[sup 3]H]mannitol (4.6 nm). Brain uptake of [[sup 14]C]hydroxyurea (8.0 ± 0.9%) was greater than [[sup 3]H]mannitol (2.4 ± 0.2%; 20-min perfusion, n = 8). CSF uptake of [[sup 14]C]hydroxyurea (5.6 ± 1.5%) was also greater than [[sup 3]H]mannitol (0.9 ± 0.3%; n = 4). Brain uptake of [[sup 14]C]hydroxyurea was increased by 200 μmhydroxyurea, 90 μmD4T, 350 μmprobenecid, 25 μmdigoxin, but not by 120 μmhydroxyurea, 16.5–50 μmD4T, 90 μm2′3′-dideoxyinosine or 90 μmabacavir. [[sup 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 brain and plasma. Results indicate that intact hydroxyurea can cross the brain barriers, but is removed from the brain by probenecid- and digoxin-sensitive transport mechanisms at the blood–brain barrier, which are also affected by D4T. These sensitivities implicate an organic anion transporter (probably organic anion transporting polypeptide 2) and possibly p-glycoprotein in the brain distribution of hydroxyurea and D4T. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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