Disposition of thymidine administered as large doses to rats and mice

Blood and urine levels of thymidine and its catabolic product, thymine, have been determined for mice and rats given a single large dose of thymidine and for rats during and after infusion of large amounts of this drug. For mice given a bolus dose (400 mg/kg, 1.2 g/m2), two phases of elimination of thymidine from blood were evident, an initial phase (half-life = 4 mins) and a longer second phase (half-life = 17 mins). The initial (2-min) level in blood was 2.8 mM. For rats given an equivalent dose (150 mg/kg, 1.2 g/m2), three phases with half-lives of 2, 29, and 365 mins were observed. The initial (5-min) concentration in the blood was 0.6 mM. More of a dose of [2-14C]thymidine was converted to CO2 by rats than by mice. For both species, small amounts of radioactivity from this labeled compound became associated with macromolecules of the small intestine. Following infusion of rats with thymidine at rates of 300 and 600 mg/kg/hr for 24 hrs (60 and 120 g/m2, respectively), steady-state blood levels were approximately 0.7 and 1.5 mM, respectively. When the infusions were stopped, a phase with a half-life of 35 mins and a longer phase of indeterminate length were noted for each dose. Elimination of metabolically formed thymine from the blood of rats and excretion into the urine was mediated by a process that was apparently saturated.