nsc-614846 and 6-aminocarbovir

Topics: Administration, Oral; Animals; Anti-HIV Agents; Dideoxynucleosides; Drug Delivery Systems; Evaluation Studies as Topic; Hepatic Veins; Infusions, Intravenous; Intestinal Absorption; Liver; Mesenteric Arteries; Models, Biological; Pharmaceutical Preparations; Portal Vein; Prodrugs; Rats

Topics: Administration, Oral; Analysis of Variance; Animals; Antiviral Agents; Catheterization, Peripheral; Cross-Over Studies; Dideoxynucleosides; Infusions, Intravenous; Injections, Intravenous; Male; Prodrugs; Rats; Rats, Sprague-Dawley

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.

Topics: Animals; Antiviral Agents; Brain; Dideoxynucleosides; Injections, Intravenous; Male; Rats; Rats, Sprague-Dawley; Time Factors