Abstract
Background and Objectives
Beraprost sodium (BPS), an orally administrable prostaglandin I2 derivative, is used for the treatment of chronic arterial occlusion and pulmonary arterial hypertension and has potential efficacy in nephropathy. Beraprost sustained release (beraprost SR) is an oral sustained-release formulation of BPS. To confirm the dose rationale reported in a multi-regional study of nephropathy patients in Asia, this open-label study evaluated ethnic differences in the pharmacokinetic profiles of BPS and its active diastereomer (BPS-314d) after beraprost SR administration among healthy Japanese, Chinese, and Korean adult males.
Methods
Twelve healthy subjects in each ethnic group were enrolled. Subjects received a single oral dose of 120 μg beraprost SR under fasting conditions.
Results
The geometric mean ratio (90% confidence interval) of the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve from time 0 to time of the last quantifiable concentration (AUClast) of BPS was 1.12 (0.85–1.48) and 1.40 (1.05–1.86) in Chinese, and 1.18 (0.90–1.55) and 1.18 (0.89–1.58) in Korean compared to Japanese subjects. These differences were not clinically relevant. Similarly, differences in the Cmax and AUClast of BPS-314d were also small among the ethnic groups. Urinary excretion of BPS and BPS-314d was limited in all ethnic groups. Together, these findings indicate that the pharmacokinetics of beraprost SR are not affected by ethnic background.
Conclusions
There were no clinically meaningful ethnic differences in the pharmacokinetics of BPS and BPS-314d following beraprost SR administration among Japanese, Chinese and Korean populations.
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Funding
This study was sponsored by Astellas Pharma Inc. and Toray Industries, Inc.
Conflict of interest
I. Nakajo, H. Inoue, M. Inaba, K. Oikawa, M Katashima, and T. Sawamoto are paid employees of Astellas Pharma Inc. H. Kurumatani is a paid employee of Toray Industries, Inc. M. Shiramoto has nothing to declare. His current affiliation is Kashiihara Hospital; this manuscript does not represent the opinions of his current affiliation.
Ethics approval
This study was approved by the Institutional Review Board (SOUSEIKAI Kyushu Clinical Pharmacology Research Clinic IRB, Fukuoka, Japan). The study was conducted in accordance with Good Clinical Practice, International Council for Harmonisation guidelines, applicable regulations and guidelines governing clinical study conduct, and the ethical principles of the Declaration of Helsinki.
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Written informed consent was obtained from all individual participants included in the study.
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Researchers may request access to anonymized participant level data, trial level data and protocols from Astellas sponsored clinical trials at http://www.clinicalstudydatarequest.com. For Astellas’ criteria for data sharing, see: http://www.clinicalstudydatarequest.com.
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Data processing, summarization, and statistical analyses were performed using SAS® version 9.1.3 and 9.4 (SAS® Institute Inc. Cary, North Carolina). Calculation of the pharmacokinetic parameters was performed using Phoenix™ WinNonlin® version 6.1 (Certara USA, Inc. Princeton, New Jersey). Figures were created using Microsoft® Excel® for Office 365 MSO.
Author contributions
Study design: IN, HI, MI, KO, MK, TS, HK, and MS. Conduct and acquisition of data: IN, HI, MI, KO, and MS. Analysis and interpretation of data: IN, HI, MI, KO, MK, TS, HK, and MS. Writing of the manuscript: IN, HI, MI, KO, MK, TS, HK, and MS.
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Nakajo, I., Inoue, H., Inaba, M. et al. Comparison of Pharmacokinetic Profiles of Beraprost Sustained Release in Japanese, Chinese, and Korean Healthy Adult Males. Clin Drug Investig 41, 549–555 (2021). https://doi.org/10.1007/s40261-021-01031-8
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DOI: https://doi.org/10.1007/s40261-021-01031-8