COMPARATIVE BRAIN EXPOSURE TO (-)-CARBOVIR AFTER (-)-CARBOVIR OR (-)-6-AMINOCARBOVIR INTRAVENOUS-INFUSION IN RATS

Purpose. Evaluate the ability of (-)-6-aminocarbovir ((-)-6AC) to impr ove the CNS exposure to (-)-carbovir ((-)-CBV). Methods. Activation of (-)-6AC in vitro was assessed by incubations of rat brain tissue homo genates. The in vivo brain exposure to (-)-CBV was then examined in ra ts after iv infusions of either (-)-CBV (n=4) or (-)-6AC (n=5). The dr ugs were infused to steady-state via the jugular vein. At the end of t he infusion, a bolus of [H-3]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 hom ogenates. After iv infusion of(-)-CBV, the brain/blood concentration r atio of (-)-CBV was 0.032 +/- 0.009. The brain/blood concentration rat io of (-)-CBV after iv infusion of (-)-6AC was 0.080 +/- 0.020. Conclu sions. (-)-6AC improved the brain delivery of (-)-CBV, although the ab solute exposure of the brain tissue to (-)-CBV was still quite low.