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Pharmacokinetics, pharmacodynamics, and safety of lesinurad, a selective uric acid reabsorption inhibitor, in healthy adult males.

Shen Z, Rowlings C, Kerr B, Hingorani V, Manhard K, Quart B, Yeh LT, Storgard C - Drug Des Devel Ther (2015)

Bottom Line: Following 400 mg qday dosing, serum uric acid reduction was 35% at 24 hours post-dose, supporting qday dosing.A relative bioavailability study in healthy males (N=8) indicated a nearly identical pharmacokinetic profile following dosing of tablets or capsules.Lesinurad was generally safe and well tolerated.

View Article: PubMed Central - PubMed

Affiliation: Ardea Biosciences, Inc. (a member of the AstraZeneca group), San Diego, CA, USA.

ABSTRACT
Lesinurad is a selective uric acid reabsorption inhibitor under investigation for the treatment of gout. Single and multiple ascending dose studies were conducted to evaluate pharmacokinetics, pharmacodynamics, and safety of lesinurad in healthy males. Lesinurad was administered as an oral solution between 5 mg and 600 mg (single ascending dose; N=34) and as an oral solution or immediate-release capsules once daily (qday) between 100 mg and 400 mg for 10 days under fasted or fed condition (multiple ascending dose; N=32). Following single doses of lesinurad solution, absorption was rapid and exposure (maximum observed plasma concentration and area under the plasma concentration-time curve) increased in a dose-proportional manner. Following multiple qday doses, there was no apparent accumulation of lesinurad. Urinary excretion of unchanged lesinurad was generally between 30% and 40% of dose. Increases in urinary excretion of uric acid and reductions in serum uric acid correlated with dose. Following 400 mg qday dosing, serum uric acid reduction was 35% at 24 hours post-dose, supporting qday dosing. A relative bioavailability study in healthy males (N=8) indicated a nearly identical pharmacokinetic profile following dosing of tablets or capsules. Lesinurad was generally safe and well tolerated.

No MeSH data available.


Related in: MedlinePlus

Median percent changes from baseline (time-matched, day −1) serum concentrations of urate following once-daily oral doses of lesinurad for 10 days.Notes: The top x-axis labels refer to the hours of that day, where “0” of the next day is the same as 24 hours of the previous day.Abbreviation: IR, immediate release.
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f2-dddt-9-3423: Median percent changes from baseline (time-matched, day −1) serum concentrations of urate following once-daily oral doses of lesinurad for 10 days.Notes: The top x-axis labels refer to the hours of that day, where “0” of the next day is the same as 24 hours of the previous day.Abbreviation: IR, immediate release.

Mentions: sUA concentrations decreased significantly over the 100 mg to 400 mg dose range, and the decreases were evident at 12 hours post-dose on day 1 (Figure 2). sUA continued to decline slowly upon repeat dosing, with maximal decreases observed within 6 to 7 days of dosing. Maximum reduction was the least with the 100 mg solution (fed) and greatest with the 200 mg capsule (fed).


Pharmacokinetics, pharmacodynamics, and safety of lesinurad, a selective uric acid reabsorption inhibitor, in healthy adult males.

Shen Z, Rowlings C, Kerr B, Hingorani V, Manhard K, Quart B, Yeh LT, Storgard C - Drug Des Devel Ther (2015)

Median percent changes from baseline (time-matched, day −1) serum concentrations of urate following once-daily oral doses of lesinurad for 10 days.Notes: The top x-axis labels refer to the hours of that day, where “0” of the next day is the same as 24 hours of the previous day.Abbreviation: IR, immediate release.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494180&req=5

f2-dddt-9-3423: Median percent changes from baseline (time-matched, day −1) serum concentrations of urate following once-daily oral doses of lesinurad for 10 days.Notes: The top x-axis labels refer to the hours of that day, where “0” of the next day is the same as 24 hours of the previous day.Abbreviation: IR, immediate release.
Mentions: sUA concentrations decreased significantly over the 100 mg to 400 mg dose range, and the decreases were evident at 12 hours post-dose on day 1 (Figure 2). sUA continued to decline slowly upon repeat dosing, with maximal decreases observed within 6 to 7 days of dosing. Maximum reduction was the least with the 100 mg solution (fed) and greatest with the 200 mg capsule (fed).

Bottom Line: Following 400 mg qday dosing, serum uric acid reduction was 35% at 24 hours post-dose, supporting qday dosing.A relative bioavailability study in healthy males (N=8) indicated a nearly identical pharmacokinetic profile following dosing of tablets or capsules.Lesinurad was generally safe and well tolerated.

View Article: PubMed Central - PubMed

Affiliation: Ardea Biosciences, Inc. (a member of the AstraZeneca group), San Diego, CA, USA.

ABSTRACT
Lesinurad is a selective uric acid reabsorption inhibitor under investigation for the treatment of gout. Single and multiple ascending dose studies were conducted to evaluate pharmacokinetics, pharmacodynamics, and safety of lesinurad in healthy males. Lesinurad was administered as an oral solution between 5 mg and 600 mg (single ascending dose; N=34) and as an oral solution or immediate-release capsules once daily (qday) between 100 mg and 400 mg for 10 days under fasted or fed condition (multiple ascending dose; N=32). Following single doses of lesinurad solution, absorption was rapid and exposure (maximum observed plasma concentration and area under the plasma concentration-time curve) increased in a dose-proportional manner. Following multiple qday doses, there was no apparent accumulation of lesinurad. Urinary excretion of unchanged lesinurad was generally between 30% and 40% of dose. Increases in urinary excretion of uric acid and reductions in serum uric acid correlated with dose. Following 400 mg qday dosing, serum uric acid reduction was 35% at 24 hours post-dose, supporting qday dosing. A relative bioavailability study in healthy males (N=8) indicated a nearly identical pharmacokinetic profile following dosing of tablets or capsules. Lesinurad was generally safe and well tolerated.

No MeSH data available.


Related in: MedlinePlus