当前位置： SCI文献检索 > Clinical and Experimental Nephrology期刊下所有文献 > Effects of mild and moderate renal dysfunction on pharmacokinetics, pharmacodynamics, and safety of dotinurad: a novel selective urate reabsorption inhibitor.

Effects of mild and moderate renal dysfunction on pharmacokinetics, pharmacodynamics, and safety of dotinurad: a novel selective urate reabsorption inhibitor.

Abstract：

BACKGROUND:Dotinurad, a novel selective urate reabsorption inhibitor, exerts a serum uric acid-lowering effect by selectively inhibiting urate transporter 1 (URAT1) in patients with hyperuricemia. It is generally known that the progression of renal dysfunction is associated with a reduction in the serum uric acid-lowering effects of uricosuric drugs. We, therefore, investigated the pharmacokinetics (PK), pharmacodynamics (PD), and safety of dotinurad in subjects with renal dysfunction. METHODS:This was a parallel-group, open-label, single-dose clinical pharmacology study. Dotinurad (1 mg) was administered once, orally to subjects with mild (estimated glomerular filtration rate [eGFR], ≥ 60 to < 90 mL/min/1.73 m2) or moderate (eGFR, ≥ 30 to < 60 mL/min/1.73 m2) renal dysfunction or normal (eGFR, ≥ 90 mL/min/1.73 m2) renal function. RESULTS:The time-course of mean plasma concentration of dotinurad had similar profiles across the groups. Regarding PK, there was no significant difference between the renal dysfunction groups and normal renal function group. Regarding PD, the maximum reduction rate in serum uric acid levels and the fractional uric acid excretion (FE) ratio (FE0-24/FE-24-0) were significantly lower in the moderate renal dysfunction group than in the normal renal function group. However, other PD parameters were not significantly different among the groups. No notable adverse events or adverse drug reactions were observed in this study. CONCLUSION:These results suggested that no dose adjustment might be necessary when administering dotinurad to patients with mild-to-moderate renal dysfunction. ClinicalTrials.gov Identifier: NCT02347046.

journal_name

Clin Exp Nephrol

journal_title

Clinical and experimental nephrology

authors

Fukase H,Okui D,Sasaki T,Fushimi M,Ohashi T,Hosoya T

doi

10.1007/s10157-019-01825-3

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

17-24

issue

Suppl 1

eissn

1342-1751

issn

1437-7799

pii

10.1007/s10157-019-01825-3

journal_volume

pub_type

临床试验,杂志文章

在线工具

Effects of mild and moderate renal dysfunction on pharmacokinetics, pharmacodynamics, and safety of dotinurad: a novel selective urate reabsorption inhibitor.