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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

Single- and multi-dose PK profiles of uridine.(a) PK profile of uridine following a single-dose of NucleomaxX® in all subjects. The solid squares indicate female subjects, and the open circles indicate male subjects. (b) PK profile of uridine following three doses of NucleomaxX® in all subjects. The solid squares indicate female subjects, and the open circles indicate male subjects.
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pone-0014709-g002: Single- and multi-dose PK profiles of uridine.(a) PK profile of uridine following a single-dose of NucleomaxX® in all subjects. The solid squares indicate female subjects, and the open circles indicate male subjects. (b) PK profile of uridine following three doses of NucleomaxX® in all subjects. The solid squares indicate female subjects, and the open circles indicate male subjects.

Mentions: At baseline (t = 0 on Day 1), mean plasma uridine level was 4.7 uM, consistent with known physiologic concentrations of this nucleoside [2]. Plasma uridine levels increased to similar maximal concentrations (>150 µM) 1–2 hours after dosing (Table 2) on both Day 1 and Day 7. The half-life of uridine after cumulative dosing was longer than that observed after a single dose (5.3±1.4 vs. 3.4±0.8 hours, p = 0.01). Plasma uridine levels at t = 0 as well as mean uridine area under the curve (AUC) and AUC∞ were greater on Day 7 than on Day 1, but the latter could be attributed to the higher baseline level of uridine on Day 7. With both the single- and multi-dose NucleomaxX® regimens, women achieved higher uridine concentrations than men (Figure 2). When plasma uridine levels were adjusted for body weight or lean body mass, the differences between men and women were no longer evident. Among the men, plasma uridine levels were higher on Day 7 compared with Day 1 at all time points (Figure 3a), but among the women, there were no significant differences in the PK profiles on days 1 and 7 (Figure 3b).


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)

Single- and multi-dose PK profiles of uridine.(a) PK profile of uridine following a single-dose of NucleomaxX® in all subjects. The solid squares indicate female subjects, and the open circles indicate male subjects. (b) PK profile of uridine following three doses of NucleomaxX® in all subjects. The solid squares indicate female subjects, and the open circles indicate male subjects.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0014709-g002: Single- and multi-dose PK profiles of uridine.(a) PK profile of uridine following a single-dose of NucleomaxX® in all subjects. The solid squares indicate female subjects, and the open circles indicate male subjects. (b) PK profile of uridine following three doses of NucleomaxX® in all subjects. The solid squares indicate female subjects, and the open circles indicate male subjects.
Mentions: At baseline (t = 0 on Day 1), mean plasma uridine level was 4.7 uM, consistent with known physiologic concentrations of this nucleoside [2]. Plasma uridine levels increased to similar maximal concentrations (>150 µM) 1–2 hours after dosing (Table 2) on both Day 1 and Day 7. The half-life of uridine after cumulative dosing was longer than that observed after a single dose (5.3±1.4 vs. 3.4±0.8 hours, p = 0.01). Plasma uridine levels at t = 0 as well as mean uridine area under the curve (AUC) and AUC∞ were greater on Day 7 than on Day 1, but the latter could be attributed to the higher baseline level of uridine on Day 7. With both the single- and multi-dose NucleomaxX® regimens, women achieved higher uridine concentrations than men (Figure 2). When plasma uridine levels were adjusted for body weight or lean body mass, the differences between men and women were no longer evident. Among the men, plasma uridine levels were higher on Day 7 compared with Day 1 at all time points (Figure 3a), but among the women, there were no significant differences in the PK profiles on days 1 and 7 (Figure 3b).

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