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Enhanced uridine bioavailability following administration of a triacetyluridine-rich nutritional supplement.

Weinberg ME, Roman MC, Jacob P, Wen M, Cheung P, Walker UA, Mulligan K, Schambelan M - PLoS ONE (2011)

Bottom Line: Single and repeated dosing with NucleomaxX® resulted in peak plasma uridine concentrations 1-2 hours later of 150.9 ± 39.3 µM and 161.4 ± 31.5 µM, respectively, levels known to ameliorate mitochondrial toxicity in vitro.No adverse effects of either treatment were observed.NucleomaxX®, containing predominantly TAU, has significantly greater bioavailability than pure uridine in human subjects and may be useful in the management of mitochondrial toxicity.

View Article: PubMed Central - PubMed

Affiliation: University of California San Francisco, San Francisco, California, United States of America. melissa.weinberg@gmail.com

ABSTRACT

Background: Uridine is a therapy for hereditary orotic aciduria and is being investigated in other disorders caused by mitochondrial dysfunction, including toxicities resulting from treatment with nucleoside reverse transcriptase inhibitors in HIV. Historically, the use of uridine as a therapeutic agent has been limited by poor bioavailability. A food supplement containing nucleosides, NucleomaxX®, has been reported to raise plasma uridine to supraphysiologic levels.

Methodology/principal findings: Single- and multi-dose PK studies following NucleomaxX® were compared to single-dose PK studies of equimolar doses of pure uridine in healthy human volunteers. Product analysis documented that more than 90% of the nucleoside component of NucleomaxX® is in the form of triacetyluridine (TAU). Single and repeated dosing with NucleomaxX® resulted in peak plasma uridine concentrations 1-2 hours later of 150.9 ± 39.3 µM and 161.4 ± 31.5 µM, respectively, levels known to ameliorate mitochondrial toxicity in vitro. C(max) and AUC were four-fold higher after a single dose of NucleomaxX® than after uridine. No adverse effects of either treatment were observed.

Conclusions/significance: NucleomaxX®, containing predominantly TAU, has significantly greater bioavailability than pure uridine in human subjects and may be useful in the management of mitochondrial toxicity.

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Related in: MedlinePlus

Structures of Uridine and 2′,3′,5′-Tri-O-acetyluridine (TAU).
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pone-0014709-g001: Structures of Uridine and 2′,3′,5′-Tri-O-acetyluridine (TAU).

Mentions: Each sachet of NucleomaxX® contained 0.58 g (1.61% by weight) uridine and 5.4 g (15.0%) 2′,3′,5′-tri-O-acetyluridine (Figure 1) as determined by HPLC-UV. The analytical method for the determination of uridine and TAU was validated according to Association of Official Analytical Chemists International guidelines for single-laboratory validation for accuracy, precision, selectivity, linearity/range, ruggedness, and limits of detection and quantitation. The identity of TAU was verified by HPLC with tandem mass spectroscopy. Uridine and TAU recoveries from NucleomaxX® were 98.2% –104.8%, and 98.3–101.5%, respectively, and repeatability precision was 2.43% relative standard deviation (RSD) for uridine, and 2.00% RSD for TAU. When the uridine and TAU content are combined, we calculated that each sachet of NucleomaxX® contained the equivalent of 1.70×10−2 mol of total uridine.


Enhanced uridine bioavailability following administration of a triacetyluridine-rich nutritional supplement.

Weinberg ME, Roman MC, Jacob P, Wen M, Cheung P, Walker UA, Mulligan K, Schambelan M - PLoS ONE (2011)

Structures of Uridine and 2′,3′,5′-Tri-O-acetyluridine (TAU).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3040752&req=5

pone-0014709-g001: Structures of Uridine and 2′,3′,5′-Tri-O-acetyluridine (TAU).
Mentions: Each sachet of NucleomaxX® contained 0.58 g (1.61% by weight) uridine and 5.4 g (15.0%) 2′,3′,5′-tri-O-acetyluridine (Figure 1) as determined by HPLC-UV. The analytical method for the determination of uridine and TAU was validated according to Association of Official Analytical Chemists International guidelines for single-laboratory validation for accuracy, precision, selectivity, linearity/range, ruggedness, and limits of detection and quantitation. The identity of TAU was verified by HPLC with tandem mass spectroscopy. Uridine and TAU recoveries from NucleomaxX® were 98.2% –104.8%, and 98.3–101.5%, respectively, and repeatability precision was 2.43% relative standard deviation (RSD) for uridine, and 2.00% RSD for TAU. When the uridine and TAU content are combined, we calculated that each sachet of NucleomaxX® contained the equivalent of 1.70×10−2 mol of total uridine.

Bottom Line: Single and repeated dosing with NucleomaxX® resulted in peak plasma uridine concentrations 1-2 hours later of 150.9 ± 39.3 µM and 161.4 ± 31.5 µM, respectively, levels known to ameliorate mitochondrial toxicity in vitro.No adverse effects of either treatment were observed.NucleomaxX®, containing predominantly TAU, has significantly greater bioavailability than pure uridine in human subjects and may be useful in the management of mitochondrial toxicity.

View Article: PubMed Central - PubMed

Affiliation: University of California San Francisco, San Francisco, California, United States of America. melissa.weinberg@gmail.com

ABSTRACT

Background: Uridine is a therapy for hereditary orotic aciduria and is being investigated in other disorders caused by mitochondrial dysfunction, including toxicities resulting from treatment with nucleoside reverse transcriptase inhibitors in HIV. Historically, the use of uridine as a therapeutic agent has been limited by poor bioavailability. A food supplement containing nucleosides, NucleomaxX®, has been reported to raise plasma uridine to supraphysiologic levels.

Methodology/principal findings: Single- and multi-dose PK studies following NucleomaxX® were compared to single-dose PK studies of equimolar doses of pure uridine in healthy human volunteers. Product analysis documented that more than 90% of the nucleoside component of NucleomaxX® is in the form of triacetyluridine (TAU). Single and repeated dosing with NucleomaxX® resulted in peak plasma uridine concentrations 1-2 hours later of 150.9 ± 39.3 µM and 161.4 ± 31.5 µM, respectively, levels known to ameliorate mitochondrial toxicity in vitro. C(max) and AUC were four-fold higher after a single dose of NucleomaxX® than after uridine. No adverse effects of either treatment were observed.

Conclusions/significance: NucleomaxX®, containing predominantly TAU, has significantly greater bioavailability than pure uridine in human subjects and may be useful in the management of mitochondrial toxicity.

Show MeSH
Related in: MedlinePlus