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Comparative Brain Exposure to (-)-Carbovir After (-)-Carbovir or (-)-6-Aminocarbovir Intravenous Infusion in Rats

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Abstract

Purpose. Evaluate the ability of (-)-6-aminocarbovir ((-)-6AC) to improve the CNS exposure to (-)-carbovir ((-)-CBV).

Methods. Activation of (-)-6AC in vitro was assessed by incubations of rat brain tissue homogenates. The in vivo brain exposure to (-)-CBV was then examined in rats after iv infusions of either (-)-CBV (n = 4) or (-)-6AC (n = 5). The drugs were infused to steady-state via the jugular vein. At the end of the infusion, a bolus of [3H]inulin was injected via the femoral vein in order to obtain an estimate of the brain vascular space.

Results. (-)-6AC was converted to (-)-CBV by incubations of rat brain tissue homogenates. After iv infusion of (-)-CBV, the brain/ blood concentration ratio of (-)-CBV was 0.032 ± 0.009. The brain/ blood concentration ratio of (-)-CBV after iv infusion of (-)-6AC was 0.080 ± 0.020.

Conclusions. (-)-6AC improved the brain delivery of (-)-CBV, although the absolute exposure of the brain tissue to (-)-CBV was still quite low.

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Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 308 Harvard St. S.E., Minneapolis, Minnesota, 55455

    Yan-Dong Wen & Cheryl L. Zimmerman

  2. Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, 308 Harvard St. S.E., Minneapolis, Minnesota, 55455

    Rory P. Remmel, Phuong T. Pham & Robert Vince

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  1. Yan-Dong Wen
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  2. Rory P. Remmel
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  4. Robert Vince
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  5. Cheryl L. Zimmerman
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Wen, YD., Remmel, R.P., Pham, P.T. et al. Comparative Brain Exposure to (-)-Carbovir After (-)-Carbovir or (-)-6-Aminocarbovir Intravenous Infusion in Rats. Pharm Res 12, 911–915 (1995). https://doi.org/10.1023/A:1016229624703

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