2018
DOI: 10.1002/jcph.1119
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Pharmacokinetics, Pharmacodynamics, and Tolerability of Concomitant Multiple Dose Administration of Verinurad (RDEA3170) and Allopurinol in Adult Male Subjects With Gout

Abstract: Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in clinical development for treatment of hyperuricemia and gout. This phase 1b, multiple‐dose, drug‐drug interaction study evaluated the pharmacokinetics, pharmacodynamics, and tolerability of verinurad in combination with allopurinol. Adult males with gout were randomized to receive once‐daily oral doses of allopurinol 300 mg or verinurad 10 mg alone for 7 days, allopurinol 300 mg + verinurad 10 mg on days 8 to 14, and the alternative single… Show more

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Cited by 15 publications
(23 citation statements)
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“…The increased urinary excretion of uric acid by verinurad may have the potential to induce uric acid microcrystallization in the renal tubules, which could increase the risk for renal-related AEs. In Phase 1 clinical trials with verinurad combined with an XOI (which reduces uric acid production), urinary excretion of uric acid was reduced, 19 , 20 which may reduce risk of microcrystallization. Reduced urinary uric acid excretion with the addition of an XOI to a URAT1 inhibitor was also seen with lesinurad, where low rates of kidney stones were observed with lesinurad + XOI treatment in Phase 3 clinical trials.…”
Section: Discussionmentioning
confidence: 99%
“…The increased urinary excretion of uric acid by verinurad may have the potential to induce uric acid microcrystallization in the renal tubules, which could increase the risk for renal-related AEs. In Phase 1 clinical trials with verinurad combined with an XOI (which reduces uric acid production), urinary excretion of uric acid was reduced, 19 , 20 which may reduce risk of microcrystallization. Reduced urinary uric acid excretion with the addition of an XOI to a URAT1 inhibitor was also seen with lesinurad, where low rates of kidney stones were observed with lesinurad + XOI treatment in Phase 3 clinical trials.…”
Section: Discussionmentioning
confidence: 99%
“…Verinurad concentrations in plasma and urine and febuxostat concentrations in plasma were measured by Ardea Biosciences, Inc. (San Diego, CA, USA). Plasma samples were extracted by protein precipitation and analytes quantified by high-performance liquid chromatography– tandem mass spectrometry [ 31 , 32 ]. Urine samples were prepared by dilution with water and quantified by high-performance liquid chromatography–tandem mass spectrometry.…”
Section: Methodsmentioning
confidence: 99%
“…All analytical methods were validated following US Food and Drug Administration bioanalytical method validation guidance [ 31 ]. The analytical methodology for the quantitation of verinurad and metabolite M1 in plasma samples was a combination method similar to the methodology described by Kankam et al [ 22 ], although that methodology did not include M1. When M1 was included in the methodology, it (and its internal standard, IS) chromatographed as diastereomers and each peak was integrated and the resulting areas summed for concentration determination.…”
Section: Methodsmentioning
confidence: 99%
“…The potency of verinurad together with its pharmacokinetic properties may enable it to be used as a low-dose drug, with potentially less drug interaction issues in gout patients receiving concurrent treatments for comorbidities such as hypertension, cardiovascular disease, diabetes, and obesity. The combination of verinurad with an XOI results in a urinary uric acid profile that may offer a low potential for renal adverse effects [ 22 ] while also lowering sUA to a greater extent than either agent alone at the same or even higher monotherapy doses [ 23 – 25 ].…”
Section: Introductionmentioning
confidence: 99%