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Erschienen in: Advances in Therapy 8/2018

02.07.2018 | Original Research

Pharmacokinetics and Safety of DS-8500a, an Antidiabetic Drug, in Japanese Subjects with Hepatic or Renal Impairment: A Single-Center, Open-Label, Single-Dose Study

verfasst von: Manabu Kato, Hitoshi Ishizuka, Takashi Taguchi, Kazuhito Shiosakai, Emi Kamiyama, Michio Sata, Takafumi Yoshida

Erschienen in: Advances in Therapy | Ausgabe 8/2018

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Abstract

Introduction

The pharmacokinetics, safety, and tolerability of DS-8500a (a G protein receptor 119 agonist) up to 100 mg have been investigated in healthy Japanese adults. The objective of this study was to evaluate the effects of hepatic or renal impairment on the pharmacokinetics of a single 25-mg oral dose of DS-8500a.

Methods

This single-center, open-label study enrolled subjects into eight groups according to hepatic function (normal; mild or moderate impairment) and renal function [normal; mild, moderate, or severe impairment; and end-stage renal disease (ESRD)]. Drug concentrations were measured by liquid-chromatography tandem mass spectrometry. Pharmacokinetic parameters were evaluated by non-compartmental analysis. Adverse events (AEs) were evaluated for safety.

Results

The hepatic and renal groups enrolled 15 and 30 subjects, respectively. Pharmacokinetic parameters of DS-8500a were comparable between the normal hepatic function and mild hepatic impairment groups, but the mean area under the concentration–time curve (AUC) was 1.37-fold higher, and the half-life was longer in the moderate hepatic impairment group compared with the normal hepatic function group. The maximum concentration (Cmax) and AUC values were 0.704- and 0.609-fold lower, respectively, in the ESRD group compared with the values in the other renal impairment groups; no clear differences in AUC and time to Cmax were observed in the normal function and mild, moderate, and severe renal impairment groups. There was no relationship between apparent total body clearance and estimated glomerular filtration rate. The incidence of AEs was similar among all groups.

Conclusion

DS-8500a exposure in the mild hepatic impairment and mild to severe renal impairment groups was similar to that in the corresponding normal hepatic and renal function groups, but dose adjustments may be required in those with moderate hepatic impairment and ESRD.

Trial registration

Japic CTI-No. 163135.

Funding

Daiichi Sankyo Co. Ltd., Tokyo, Japan.
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Metadaten
Titel
Pharmacokinetics and Safety of DS-8500a, an Antidiabetic Drug, in Japanese Subjects with Hepatic or Renal Impairment: A Single-Center, Open-Label, Single-Dose Study
verfasst von
Manabu Kato
Hitoshi Ishizuka
Takashi Taguchi
Kazuhito Shiosakai
Emi Kamiyama
Michio Sata
Takafumi Yoshida
Publikationsdatum
02.07.2018
Verlag
Springer Healthcare
Erschienen in
Advances in Therapy / Ausgabe 8/2018
Print ISSN: 0741-238X
Elektronische ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-018-0739-4

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