Pharmacokinetics of the Antiviral Agent β-d-2′,3′-Didehydro-2′,3′-Dideoxy-5-Fluorocytidine in Rhesus Monkeys

The values of the pharmacokinetic parameters of the nucleoside antiretroviral agent β-d-2′,3′-didehydro-2′,3′-dideoxy-5-fluorocytidine (D-D4FC) in rhesus monkeys were determined with a two-compartment model after the administration of a single dose. The average values for the terminal half-life, renal clearance, and total systemic clearance for the intravenous administration 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 administration route, 76% of the compound was recovered intact in the urine within 8 h, indicating that D-D4FC was eliminated mainly by renal excretion. D-D4FC was detected in the cerebrospinal fluid (CSF) at similar concentrations after administration by both the intravenous and oral routes. D-D4FC levels in plasma and CSF were higher than the median effective concentration for human immunodeficiency virus type 1 in vitro.