title: Comparative brain exposure to (-)-carbovir after (-)-carbovir or (-)-6-aminocarbovir intravenous infusion in rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis 55455, USA.
authors.forename: Y D
authors.initials: YD
authors.lastname: Wen
authors.forename: R P
authors.initials: RP
authors.lastname: Remmel
authors.forename: P T
authors.initials: PT
authors.lastname: Pham
authors.forename: R
authors.initials: R
authors.lastname: Vince
authors.forename: C L
authors.initials: CL
authors.lastname: Zimmerman
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D015224:Dideoxynucleosides / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D015224:Dideoxynucleosides; C057503:carbovir; C069735:6-aminocarbovir