PHARMACOKINETICS OF THE ANTIVIRAL AGENT CARBOCYCLIC 3-DEAZAADENOSINE

The pharmacokinetics of carbocyclic 3-deazaadenosine (Cc3Ado), a compe titive inhibitor of S-adenosyl-L-homocysteine hydrolase and novel anti viral agent, was investigated in female BALB/c mice. Mice were dosed e ither orally or intravenously with a single dose of 10 mg/kg (10 muCi [H-3]Cc3Ado), and blood and tissue samples were taken at selected inte rvals for 24 hr. The plasma concentration vs. time data for Cc3Ado was best described by a two-compartment open model with first-order elimi nation. The apparent half-life was 23 and 38 min, for intravenously an d orally administered Cc3Ado, respectively. Depending on route, tissue concentrations of Cc3Ado reached their maximum by 120 min, and concen trations of Cc3Ado were greatest in the liver, followed by the kidney, spleen, and stomach. By 24 hr, all tissues contained a similar amount of Cc3Ado. In the plasma, one major labeled metabolite was detected, which increased in concentration over time until about 45 min after do sing. None of the plasma Cc3Ado was protein bound, as assessed by in v itro protein binding analysis. Oral Cc3Ado was about 20% bioavailable. Data from this first investigation of the pharmacokinetics of Cc3Ado indicate that this antiviral agent is rapidly distributed and eliminat ed from the plasma and that distribution to tissues is wide-spread and rapid.