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

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.