Pharmacokinetics of the Antiviral Agent β- l -3′-Fluoro-2′,3′-Didehydro-2′,3′-Dideoxycytidine in Rhesus Monkeys

Pharmacology and Pharmacokinetics of the Antiviral Agent β-d-2′,3′-Dideoxy-3′-Oxa-5-Fluorocytidine in Cells and Rhesus Monkeys

“…(Table 2), which is higher than other nucleoside RT inhibitors (2,3). Approximately 72% of the absorbed dose was recovered unchanged in the urine after oral administration in monkeys (CL R /CL T ).…”

l-Pentoses in Biological and Medicinal Applications

“…Nevertheless, a chemical and enzymatic stability study demonstrated that the 3′-F substitution stabilized the glycosyl bond. A pharmacokinetic study in three rhesus monkeys following single-dose oral administration of 3′F-β- l- d4C showed a mean maximum plasma concentration ( C max ) = 4.4 μg/mL and time of maximum concentration ( T max ) = 1.67 h . The concentration of 3′F-β- l- d4C in the plasma of rhesus monkeys remained higher than the EC 90 value against wild-type HIV-1 12 h after the oral doses.…”

Developments in Antiviral Drug Design, Discovery and Development in 2004

“…The pharmacokinetic properties in rhesus monkeys of L-3'-F-d4C (82), a potent inhibitor of HIV and HBV, have been described [315]. While the compound was orally bioavailable, variability in exposure was observed that was not abrogated by coadministration with sodium bicarbonate solution as a basic buffer to reduce the potential for hydrolytic cleavage of the sugar ring [315].…”

“…The pharmacokinetic properties in rhesus monkeys of L-3'-F-d4C (82), a potent inhibitor of HIV and HBV, have been described [315]. While the compound was orally bioavailable, variability in exposure was observed that was not abrogated by coadministration with sodium bicarbonate solution as a basic buffer to reduce the potential for hydrolytic cleavage of the sugar ring [315]. Structure-activity relationships for L-3'Fd4C (82) have revealed that the enantiomer with a natural sugar configuration, D-3'F-d4C (83), inhibited HIV-1 replication in cell culture with an EC 50 = 2.3 µM, over 25-fold weaker than for 82 [316].…”