Pharmacokinetics of the antiviral agent beta-D-2 ',3 '-didehydro-2 ',3 '-dideoxy-5-fluorocytidine in rhesus monkeys

The values of the pharmacokinetic parameters of the nucleoside antiretrovir al agent beta-D-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine (D-D4FC) in rhesus monkeys were determined with a two-compartment model after the admin istration of a single dose. The average values for the terminal half-life, renal clearance, and total systemic clearance for the intravenous administr ation route were 3.6 h and 0.31 and 0.43 liter.kg(-1).h(-1), respectively. The oral bioavailability of D-D4FC averaged 41%. For the intravenous admini stration route, 76% of the compound was recovered intact in the urine withi n 8 h, indicating that D-D4FC was eliminated mainly by renal excretion. D-D 4FC was detected in the cerebrospinal fluid (CSF) at similar concentrations after administration by both the intravenous and oral routes. D-D4FC level s in plasma and CSF were higher than the median effective concentration for human immunodeficiency virus type 1 in vitro.