Comparison of the bioavailability of uridine in mice after either oral or parenteral administration

Summary

We compared the bioavailability of uridine (Urd) (350 and 3500 mg/kg) administered either as a single SC injection or by gavage, in male CD8F₁ mice. Plasma samples were analyzed for Urd and uracil (Ura) using high-pressure liquid chromatography. After Urd (3500 mg/kg, SC), plasma Urd levels peaked at 4900 μM and then declined to pretreatment levels (< 10 μM) within 6h. Plasma Ura concentrations peaked at 1400 μM and then declined initially more slowly than Urd. After Urd (3500 mg/kg, PO) plasma levels of Urd were fairly constant (range 33–82 μM) for up to 8 h and had returned to pretreatment levels at 16 h. Plasma Ura concentrations paralleled Urd, but were approxximately ten-fold higher. Areas under the concentration-time curve for Urd showed that the bioavailability of Urd after PO administration was 7% of that after SC administration. After Urd (350 mg/kg, SC) Urd levels peaked at 210 μM returning to pretreatment levels within 2 h. Plasma Ura levels reached a peak with 300 μM and then declined initially more slowly than those of Urd. After Urd (350 mg/kg, PO) plasma Urd levels were not perturbed, although Ura levels peaked at 50 μM after which they declined and could no longer be detected at 4 h. These data indicate that (a) the bioavailability of Urd (350 or 3500 mg/kg) was lower when given PO than when it was administered by SC injection; and (b) Urd (3500 mg/kg) PO resulted in prolonged and relatively constant plasma Urd levels compared with Urd (3500 mg/kg) SC. These results suggest that Urd PO should be compared with parenterally administered Urd in attempts to increase the therapeutic index of 5-fluorouracil and of antimetabolite inhibitors of de novo pyrimidine biosynthesis.