Comparative brain exposure to (-)-carbovir after (-)-carbovir or (-)-6-aminocarbovir intravenous infusion in rats.
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.
Wen
Y D
YD
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis 55455, USA.
Remmel
R P
RP
Pham
P T
PT
Vince
R
R
Zimmerman
C L
CL
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
D000998:Antiviral Agents; D015224:Dideoxynucleosides; C057503:carbovir; C069735:6-aminocarbovir