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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 ┬ÁM and 161.4 ┬▒ 31.5 ┬ÁM, 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

PK profile of uridine after single doses of NucleomaxX® and pure uridine in all subjects.An equimolar amount of NucleomaxX® and pure uridine (RG2417) was used. The solid diamonds indicate NucleomaxX®, and the open diamonds indicate pure uridine.
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pone-0014709-g004: PK profile of uridine after single doses of NucleomaxX® and pure uridine in all subjects.An equimolar amount of NucleomaxX® and pure uridine (RG2417) was used. The solid diamonds indicate NucleomaxX®, and the open diamonds indicate pure uridine.

Mentions: Mean plasma uridine level prior to drug administration (tÔÇŐ=ÔÇŐ0) was similar in both PK studies (4.1┬▒1.4 vs. 4.7┬▒2.1 uM, for the uridine and NucleomaxX┬« studies, respectively; pÔÇŐ=ÔÇŐNS). When the single-dose uridine PK profile of NucleomaxX┬« (containing predominantly TAU) was compared with that of pure uridine using the same PK protocol and laboratory assay, four-fold greater bioavailability was observed with NucleomaxX┬«. The maximal uridine concentration, AUC, and AUCÔł× were significantly higher in both men and women (Table 2 and Figure 4). The mean maximal concentration of uridine after administration of pure uridine was 36.1┬▒11.3 ┬ÁM compared with 150.9┬▒39.3 ┬ÁM after NucleomaxX┬« (p<0.0001), also occurring 1ÔÇô2 hours after dosing. The half-life for pure uridine was longer than that for NucleomaxX┬« (4.6┬▒1.2 vs. 3.4┬▒0.8 hours, pÔÇŐ=ÔÇŐ0.05).


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)

PK profile of uridine after single doses of NucleomaxX® and pure uridine in all subjects.An equimolar amount of NucleomaxX® and pure uridine (RG2417) was used. The solid diamonds indicate NucleomaxX®, and the open diamonds indicate pure uridine.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0014709-g004: PK profile of uridine after single doses of NucleomaxX® and pure uridine in all subjects.An equimolar amount of NucleomaxX® and pure uridine (RG2417) was used. The solid diamonds indicate NucleomaxX®, and the open diamonds indicate pure uridine.
Mentions: Mean plasma uridine level prior to drug administration (tÔÇŐ=ÔÇŐ0) was similar in both PK studies (4.1┬▒1.4 vs. 4.7┬▒2.1 uM, for the uridine and NucleomaxX┬« studies, respectively; pÔÇŐ=ÔÇŐNS). When the single-dose uridine PK profile of NucleomaxX┬« (containing predominantly TAU) was compared with that of pure uridine using the same PK protocol and laboratory assay, four-fold greater bioavailability was observed with NucleomaxX┬«. The maximal uridine concentration, AUC, and AUCÔł× were significantly higher in both men and women (Table 2 and Figure 4). The mean maximal concentration of uridine after administration of pure uridine was 36.1┬▒11.3 ┬ÁM compared with 150.9┬▒39.3 ┬ÁM after NucleomaxX┬« (p<0.0001), also occurring 1ÔÇô2 hours after dosing. The half-life for pure uridine was longer than that for NucleomaxX┬« (4.6┬▒1.2 vs. 3.4┬▒0.8 hours, pÔÇŐ=ÔÇŐ0.05).

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 ┬ÁM and 161.4 ┬▒ 31.5 ┬ÁM, 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