Clinical pharmacological study of dotinurad administered to male and female elderly or young subjects

Hiroshi Nakatani, Masahiko Fushimi, Tomomitsu Sasaki, Daisuke Okui, Tetsuo Ohashi, Hiroshi Nakatani, Masahiko Fushimi, Tomomitsu Sasaki, Daisuke Okui, Tetsuo Ohashi

Abstract

Background: Dotinurad is a novel selective urate reabsorption inhibitor (SURI) that selectively inhibits the reabsorption of uric acid in renal tubules and promotes the excretion of uric acid into urine. In this study, the effects of age and gender on the pharmacokinetics (PK), pharmacodynamics (PD), and safety of dotinurad were evaluated in healthy subjects.

Methods: An open-label study of a single oral administration of dotinurad 1 mg was conducted in elderly (≥ 65 years) Japanese males and females, and young (20-35 years) males and females (six patients each).

Results: Following a single-dose administration of dotinurad, the change in dotinurad plasma concentration showed a similar profile across groups. Regarding the PK parameters, there was no significant difference between elderly and young subjects. On comparing males and females, significant differences were observed in some parameters in elderly subjects. However, these differences in some parameters could not be detected by adjust for body weight. When PD parameters in elderly and young subjects were compared, significant differences were observed in some parameters in male subjects. On comparing males and females, significant differences were observed in some parameters in young subjects; however, the percent change in serum uric acid concentration decreased over time was relatively close for both groups. There were no clinically relevant safety problems.

Conclusion: Age and gender had no clinically meaningful effect on the PK, PD, and safety of dotinurad.

Clinical trials: ClinicalTrials.gov identifier: NCT02344875.

Keywords: Age; Dotinurad; Gender; Pharmacodynamics; Pharmacokinetics; Selective urate reabsorption inhibitor.

Conflict of interest statement

Fuji Yakuhin Co., Ltd. (Fuji) the manufacturer of dotinurad sponsored this study. NH was investigator in this study and received manuscript fees from Fuji. The other authors were employees of Fuji.

Figures

Fig. 1
Fig. 1
Time course of dotinurad concentrations. Error bars indicate standard deviation
Fig. 2
Fig. 2
Time course of serum uric acid concentrations. Error bars indicate standard deviation

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