(-)-6-Aminocarbovir pharmacokinetics and relative carbovir exposure in rats.
The potential for the metabolic conversion of (-)-6-aminocarbovir to (-)-carbovir, a potent reverse transcriptase inhibitor effective against human immunodeficiency virus, has been examined in male Sprague-Dawley rats. Plasma (-)-6-aminocarbovir concentrations declined rapidly in a biphasic manner following an iv bolus dose of 20 mg/kg. The total systemic clearance was 5.4 liter/hr/kg and the terminal t1/2 was 0.35 hr. Following iv dosing, approximately half of the dose was excreted into the urine and comprised equivalent quantities of (-)-carbovir and (-)-6-aminocarbovir. Orally administered (-)-6-aminocarbovir was rapidly absorbed (tmax of 0.39 hr and Cmax of 4.96 micrograms/ml) following a 60 mg/kg dose. Following oral administration, 32% of the dose was eliminated in the urine, and comprised (-)-carbovir (75%) and (-)-6-aminocarbovir (25%). The oral bioavailability of (-)-6-aminocarbovir was 46% by plasma AUC comparison and 33% based on urinary excretion data. Exposure to (-)-carbovir was lower following (-)-6-aminocarbovir dosing than observed following (-)-Carbovir dosing, by both the oral and iv routes.
Drug Metabolism, Glaxo Inc., Research Triangle Park, NC 27709.
R L
RL
Yeager
K R
KR
Brouwer
G T
GT
Miwa
D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D015224:Dideoxynucleosides / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D011355:Prodrugs / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D011355:Prodrugs; C057503:carbovir; C069735:6-aminocarbovir