Pharmacokinetics, Pharmacodynamics, and Safety Evaluation of the Novel HIF-PH Inhibitor Enarodustat: An Open-Label Phase I Study in Healthy Chinese Participants.

IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Clinical Drug Investigation Pub Date : 2025-03-13 DOI:10.1007/s40261-025-01428-9
Cheng Cui, Xiaoye Niu, Haiyan Li, Ruijie Zhang, Lei Geng, Wei Lin, Zichen Liu, Xiaohong Wang, Dongyang Liu
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Abstract

Background and objectives: Enarodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor. We evaluated the pharmacokinetics, pharmacodynamics, and safety profile of domestic enarodustat (SAL-0951) and analyzed the influence of ethnic factors.

Methods: In this phase I study, healthy Chinese participants received single and multiple oral doses (1, 5, and 15 mg) of SAL-0951 while in a fasted state. We monitored the pharmacokinetics, pharmacodynamics, and safety characteristics and analyzed the impact of ethnicity on pharmacokinetic characteristics.

Results: In total, 33 healthy Chinese participants were enrolled; the mean age was 31.2 ± a standard deviation of 5.5 years. After single doses of 1, 5, and 15 mg were administered under fasted conditions, SAL-0951 was rapidly absorbed. Mean maximum plasma concentration and area under the plasma concentration-time curve from time 0 to the last quantifiable concentration increased dose proportionately from 0.14 to 2.54 μg/mL and from 0.63 to 9.50 h × μg/mL, respectively. The elimination half-life was 6.13, 6.32, and 6.74 h, respectively, in these three groups, and the mean value of apparent clearance ranged from 1.64 to 1.89 L/h. SAL-0951 was excreted mostly as the parent compound. It reached a stable concentration after 5 days of multiple-dose administration. We observed no drug accumulation or time-dependent pharmacokinetic characteristics and no significant difference in pharmacokinetic characteristics between Chinese and Japanese participants.

Conclusion: SAL-0951 was safe and well tolerated in healthy Chinese participants and had a linear pharmacokinetic profile. We found no ethnic differences in the pharmacokinetic characteristics of the drug between Chinese and Japanese populations.

Clinical trial registration: Registered at Chinadrugtrials.org.cn, registration number CTR2020245.

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来源期刊
CiteScore
5.90
自引率
3.10%
发文量
108
审稿时长
6-12 weeks
期刊介绍: Clinical Drug Investigation provides rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. The Journal includes: -Clinical trials, outcomes research, clinical pharmacoeconomic studies and pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs. -Clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice. -Pharmacodynamic and pharmacokinetic studies in healthy volunteers in which significant implications for clinical prescribing are discussed. -Studies focusing on the application of drug delivery technology in healthcare. -Short communications and case study reports that meet the above criteria will also be considered. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Clinical Drug Investigation may be accompanied by plain language summaries to assist readers who have some knowledge, but non in-depth expertise in, the area to understand important medical advances.
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