Enhanced Uridine Bioavailability Following Administration of a Triacetyluridine-Rich Nutritional Supplement

Background: Uridine is a therapy for hereditary orotic aciduria and is being investigated in other disorders caused by dysfunction, including toxicities resulting from treatment with nucleoside reverse transcriptase inhibitors in Historically, the use of uridine as a therapeutic agent has been limited by poor bioavailability. A food supplement nucleosides, NucleomaxX (R), has been reported to raise plasma uridine to supraphysiologic levels. Methodology/Principal Findings: Single-and multi-dose PK studies following NucleomaxX (R) were compared to single-dose studies of equimolar doses of pure uridine in healthy human volunteers. Product analysis documented that more than of the nucleoside component of NucleomaxX (R) is in the form of triacetyluridine (TAU). Single and repeated dosing with NucleomaxX (R) resulted in peak plasma uridine concentrations 1-2 hours later of 150.9 +/- 39.3 mu M and 161.4 +/- 31.5 mu M, respectively, levels known to ameliorate mitochondrial toxicity in vitro. C(max) and AUC were four-fold higher after a single of NucleomaxX (R) than after uridine. No adverse effects of either treatment were observed. Conclusions/Significance: NucleomaxX (R), containing predominantly TAU, has significantly greater bioavailability than pure in human subjects and may be useful in the management of mitochondrial toxicity.