BIOAVAILABILITY AND PHARMACOKINETIC PARAMETERS FOR 5-ETHYL-2'-DEOXYURIDINE

Pharmacokinetic parameters for 5-ethyl-2'-deoxyuridine (EDU) were dete rmined following intravenous (iv) and oral (po) dosing in male Balb-e mice and iv dosing in male Sprague-Dawley rats. The concentrations of EDU in blood after 100 mg/kg iv bolus injections into mice and rats we re consistent with a two compartment kinetic model. Based on this kine tic model, EDU showed a very short distribution half-life of 1.4 +/- 0 .7 min in mice and 1.3 +/- 0.1 min in rats. The elimination half-life of EDU in rats following iv bolus injection, was substantially (18.5 /- 1.0 min) shorter than that in mice (24.1 +/- 2.9 min). The mean res idence time (MRT) of EDU was also substantially longer in mice (25.8 /- 4.9 min) compared to rats (11.0 +/- 2.9 min). However, clearance of EDU was similar in both rats and mice. Although the biotransformation of EDU was similar in mice and rats, cleavage of the EDU glycoside bo nd was less extensive in mice than in rats. EDU showed a 49% bioavaila bility in mice after a 100 mg/kg po dose. The concentration of EDU in blood after a po dose provided the best fit to a one compartment model . The maximum blood concentration of EDU (C-max was 2.4 +/- 0.2 mu g/g of blood which attained 31.1 +/- 1.2 min (T-max) after a 100 mg/kg po dose. The AUC of 5-ethyluracil (EU) after a po dose of EDU was signif icantly higher (P < 0.05) than after an iv dose of EDU. This observati on indicates that EDU undergoes degradation by phosphorylases present in the gastrointestinal tract and/or by presystemic metabolism.