Evaluation of Uricosuric Agents in Chronic Gout

Ogryzlo, M. A.; Harrison, Joan E.

doi:10.1136/ard.16.4.425

Cited by 38 publications

(14 citation statements)

References 22 publications

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“…The most common urate-lowering strategies include reducing urate production with xanthine oxidase inhibitors, such as allopurinol and febuxistat (11,12), and enhancing uric acid urinary excretion with uricosuric agents, such as probenecid, sulfinpyrazone, and benzbromarone. The percentage of reduction from initial blood urate is around 31.7% for allopurinol (4), 44.7-51.5% for febuxistat (11), 58.3% for benzbromarone (4), and 23% for probenecid (13). It should be noted that, for all of the urate-lowering compounds mentioned above, their use is limited due to their less favorable safety or efficacy profiles.…”

Section: Discussionmentioning

confidence: 99%

Erratum to: Population Pharmacokinetics and Exposure-Uric Acid Analyses After Single and Multiple Doses of ABT-639, a Calcium Channel Blocker, in Healthy Volunteers

Liu

Duan

et al. 2015

AAPS J

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The PDF version of the published article contains errors throughout the text, which were introduced by the typesetter when performing the author's proof corrections. This erratum contains the corrected PDF.The online version of the original article can be found at http:// dx.doi.org/10.1208/s12248-014-9709-1. Abstract. ABT-639 is a selective T-type calcium channel blocker with efficacy in a wide range of preclinical models of nociceptive and neuropathic pain. In the current first-in-human (FIH) study, the pharmacokinetics, tolerability, and safety of ABT-639 after single-(up to 170 mg) and multiple doses (up to 160 mg BID) were evaluated in healthy volunteers in a randomized, double-blinded, placebocontrolled manner. ABT-639 demonstrated acceptable safety and pharmacokinetic profiles in human.Results from assessment of the routine laboratory variables showed an unexpected statistically significant and clinically relevant decrease in blood uric acid with the increase in ABT-639 dose, which is possibly due to inhibition in URAT1 transporter. Pharmacokinetic/pharmacodynamic models were constructed to characterize the relationship between ABT-639 exposure and uric acid response.The final model was a mechanism-based indirect response pharmacodynamic model with the stimulation of uric acid elimination by ABT-639. The model estimated K in values in males and females were 10.2 and 7.13 μmol/h, respectively. The model estimated K out was 0.033 1/h. ABT-639 concentration that can produce 50% stimulation in uric acid elimination was estimated to be 8,070 ng/mL. Based on the final model, further simulations were conducted to predict the effect of ABT-639 on uric acid in gout patients. The simulation results indicated that, if the urate-lowering response to ABT-639 in gout patients is similar to that in healthy subjects, ABT-639 BID doses of 140 mg or higher would be expected to provide clinically meaningful lowering of blood uric acid levels below the 380 μmol/L solubility limit of monosodium urate.

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Section: Discussionmentioning

confidence: 99%

Erratum to: Population Pharmacokinetics and Exposure-Uric Acid Analyses After Single and Multiple Doses of ABT-639, a Calcium Channel Blocker, in Healthy Volunteers

Liu

Duan

et al. 2015

AAPS J

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“…Heterozyklische Verbindungen, so das wegen seiner Toxizität nicht m ehr benutzte Atophan sowie das Phenylbutazon [8,68,107,124] bzw. ein, durch eine Phenylsulfinyläthylgruppe substituierter M etabolit, der nur noch urikusurisch, nicht mehr antiphlogistisch und natrium retinierend wirkt [125][126][127][128]132], das A nturan (Geigy).…”

Section: Tagung 210unclassified

Die Gicht

Schwarting¹

1962

Digestion

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“…von K e r s l e y und Mitarb. (11-13 ) , B o r r a c h e r o d e l C ampo (17), M oreno (16), O g r y z l o (18,19), D e l b a r r e (20), Se r r e (21,22), G utm an und Y ü (23), Yü, B u r n s und G utm an (24).…”

Section: P H E N Y Lb U Ta Z O N ( a N T Ip H Lo G Is T Is C H U N unclassified

Zur uricosurischen Wirkung eines Sulfoxydanalogen des Phenylbutazons

Jungbluth¹,

Martin²

1961

Chemotherapy

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Evaluation of Uricosuric Agents in Chronic Gout

Cited by 38 publications

References 22 publications

Erratum to: Population Pharmacokinetics and Exposure-Uric Acid Analyses After Single and Multiple Doses of ABT-639, a Calcium Channel Blocker, in Healthy Volunteers

Erratum to: Population Pharmacokinetics and Exposure-Uric Acid Analyses After Single and Multiple Doses of ABT-639, a Calcium Channel Blocker, in Healthy Volunteers

Die Gicht

Zur uricosurischen Wirkung eines Sulfoxydanalogen des Phenylbutazons

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