Kinetics of ddI in Plasma, Brain, and CSF of Rats after Administration of ddI and an Ester Prodrug of ddI

Kinetics of ddI in Plasma, Brain, and CSF of Rats after Administration of ddI and an Ester Prodrug of ddI

The clinical course of AIDS dementia complex can be correlated with HIV replication in the CNS, suggesting a need for antiviral drugs that readily cross the blood-brain barrier. The present study was undertaken to characterize the pharmacokinetic parameters of dideoxyinosine (ddI) in plasma, brain,...

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Veröffentlicht in:Annals of the New York Academy of Sciences 1990-12, Vol.616 (1), p.472-474
Hauptverfasser: ANDERSON, BRADLEY D., HOESTEREY, BARBARA L., BAKER, DAVID C., GALINSKY, RAYMOND E.
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container_issue 1
container_start_page 472
container_title Annals of the New York Academy of Sciences
container_volume 616
creator ANDERSON, BRADLEY D.
HOESTEREY, BARBARA L.
BAKER, DAVID C.
GALINSKY, RAYMOND E.
description The clinical course of AIDS dementia complex can be correlated with HIV replication in the CNS, suggesting a need for antiviral drugs that readily cross the blood-brain barrier. The present study was undertaken to characterize the pharmacokinetic parameters of dideoxyinosine (ddI) in plasma, brain, and CSF after administration of ddI and to compare these with the same parameters obtained after administration of ddI-5'-butyrate ester. During a two hour infusion of ddI in male Sprague-Dawley rats at a rate of 130 mg/kg/h, steady-state plasma concentrations of 50 mu g/mL were obtained within 30 minutes. After the infusions were terminated, ddI decline biphasically from plasma with alpha t1/2 = 3 minutes and beta t1/2 = 5 minutes. Steady-state concentrations of ddI in brain tissue and CSF were 4.7% and 1.5% of plasma concentrations, respectively. The higher percentage found in brain tissue was attributed primarily to the contribution of vascular blood in brain tissue (ca. 4%).
doi_str_mv 10.1111/j.1749-6632.1990.tb17867.x
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title Kinetics of ddI in Plasma, Brain, and CSF of Rats after Administration of ddI and an Ester Prodrug of ddI
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