Pharmaceutical Research 1995-06-01

Comparative brain exposure to (-)-carbovir after (-)-carbovir or (-)-6-aminocarbovir intravenous infusion in rats.

Y D Wen, R P Remmel, P T Pham, R Vince, C L Zimmerman

Index: Pharm. Res. 12(6) , 911-5, (1995)

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Abstract

Evaluate the ability of (-)-6-aminocarbovir ((-)-6AC) to improve the CNS exposure to (-)-carbovir ((-)-CBV).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.(-)-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.(-)-6AC improved the brain delivery of (-)-CBV, although the absolute exposure of the brain tissue to (-)-CBV was still quite low.