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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 plasma concentration profiles from 0 to 24 hours post-dose following single doses of lesinurad: tablet versus capsule in healthy fed male subjects.Abbreviation: IR, immediate release.
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f3-dddt-9-3423: Median plasma concentration profiles from 0 to 24 hours post-dose following single doses of lesinurad: tablet versus capsule in healthy fed male subjects.Abbreviation: IR, immediate release.

Mentions: The median plasma concentration–time profiles for single oral doses of 400 mg lesinurad capsule and 200, 400, and 600 mg lesinurad tablets are shown in Figure 3. Lesinurad exposure (Cmax and AUC[0–inf]) increased in a dose-related manner from the 200 mg to the 600 mg tablets (Table S2). Systemic exposure of lesinurad was nearly identical following oral administration of the capsules and tablets at the 400 mg dose, with a geometric mean ratio (90% CI) for Cmax of 101 (89.2; 115) and 97.8 (89.6; 107) for AUC(0–inf). The median Tmax was generally similar between the capsule and the tablet. The amount of lesinurad excreted in urine increased in a dose-related manner and was the same with the 400 mg capsule and the 400 mg tablet. Fractional excretion and renal clearance of lesinurad were similar across all doses and both formulations.


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 plasma concentration profiles from 0 to 24 hours post-dose following single doses of lesinurad: tablet versus capsule in healthy fed male subjects.Abbreviation: IR, immediate release.
© Copyright Policy
Related In: Results  -  Collection

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

f3-dddt-9-3423: Median plasma concentration profiles from 0 to 24 hours post-dose following single doses of lesinurad: tablet versus capsule in healthy fed male subjects.Abbreviation: IR, immediate release.
Mentions: The median plasma concentration–time profiles for single oral doses of 400 mg lesinurad capsule and 200, 400, and 600 mg lesinurad tablets are shown in Figure 3. Lesinurad exposure (Cmax and AUC[0–inf]) increased in a dose-related manner from the 200 mg to the 600 mg tablets (Table S2). Systemic exposure of lesinurad was nearly identical following oral administration of the capsules and tablets at the 400 mg dose, with a geometric mean ratio (90% CI) for Cmax of 101 (89.2; 115) and 97.8 (89.6; 107) for AUC(0–inf). The median Tmax was generally similar between the capsule and the tablet. The amount of lesinurad excreted in urine increased in a dose-related manner and was the same with the 400 mg capsule and the 400 mg tablet. Fractional excretion and renal clearance of lesinurad were similar across all doses and both formulations.

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