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Pharmacokinetics of Henagliflozin in Dialysis Patients with Diabetes

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Abstract

Aim

This study aimed to assess the pharmacokinetics of henagliflozin in dialysis patients with diabetes.

Methods

In this prospective, randomized, open-label study where 10 hemodialysis and 10 peritoneal dialysis patients with diabetes were randomized in a 1:1:1:1 ratio to oral administration of henagliflozin in doses of 5 and 10 mg/day. The pharmacokinetics of a single dose of henagliflozin on Days 1 and 2, the minimum plasma concentration (Cmin) of the steady state on Day 10, and single hemodialysis clearance of henagliflozin were measured.

Results

The mean values of Cmax were 70.2–77.0 ng/mL and 105–143 ng/mL in the 5 mg and 10 mg henagliflozin groups, respectively; the mean values of AUCinf were 777–811 h*ng/mL and 1290–1730 h*ng/mL in the 5 mg and 10 mg henagliflozin groups, respectively. The median Tmax values ranged from 1 to 3 h across the dose range. The mean values of T1/2 of henagliflozin were 14.1–14.5 and 16.2–21.0 h in the 5 mg and 10 mg groups, respectively. The Cmin values of the steady state in dialysis patients taking 5 mg and 10 mg of henagliflozin were 15.0 ± 4.4 ng/mL and 26.8 ± 16.3 ng/mL, respectively, which were 123.8% and 131.0% higher than those in diabetic patients with normal renal function, respectively. Henagliflozin concentration was decreased by 1.1% after hemodialysis treatment. No treatment-related serious adverse events or discontinuations occurred.

Conclusions

Henagliflozin at the current recommended dosage may be safe, although it is possible to result in slight accumulation in patients on dialysis.

Registration

Chinese Clinical Trial Registry number ChiCTR2200062872. The date of registration: August 22, 2022.

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Acknowledgments

We thank the nurses who administered medicines and Miss Yini Jiang for double-checking the data. Miss Jiang received no financial support for her participation. We also appreciate the volunteers who willingly participated and were involved in this study. Leyi Gu was funded by the Program of Shanghai Academic/Technology Research Leader (22XD1431400), the Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant (20172015), and the National Nature Science Foundation Grant of China (81970610).

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Author notes

  1. Li Ding and Shang Liu contributed equally to the writing of this article.

Authors and Affiliations

  1. Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Renji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, 160# Pujian Road, Building 3, 12th Floor, Shanghai, 200127, China

    Li Ding, Shang Liu, Hao Yan, Zhenyuan Li, Yijun Zhou, Huihua Pang, Renhua Lu, Weiming Zhang, Miaolin Che, Lin Wang, Qin Wang, Wei Fang, Minfang Zhang, Xiajing Che & Leyi Gu

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  1. Li Ding
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Corresponding author

Correspondence to Leyi Gu.

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Funding

Science and technology Commission of Shanghai municipality and Shanghai Hengrui pharmaceutical Co. Ltd.

Conflicts of Interest

Leyi Gu worked with Shanghai Hengrui Pharmaceutical Co. Ltd. as a consultant and did not receive any remuneration or funding from the company. Li Ding, Shang Liu, Hao Yan, Zhenyuan Li, Yijun Zhou, Huihua Pang, Renhua Lu, Weiming Zhang, Miaolin Che, Lin Wang, Qin Wang, Wei Fang, Minfang Zhang, and Xiajing Che declared no conflicts of interest that might be relevant to this work.

Contribution Statement

L.G Designed the study. LD, SL, HY, ZL, YZ, and HP recruited patients and were responsible for the informed consent form signing process. LD, SL, HY, ZL, HP, RL, WZ, MC, LW, WF, QW, MZ, XC, and LG followed up with patients. LD, SL, and LG conducted the data analysis. LD and SL wrote the first draft of the manuscript, and LG edited the manuscript. LG is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Data Availability

The original contributions presented in the study are included in the Supplementary Material. Further inquiries can be directed to the corresponding authors.

Ethics Approval

Ethics Committee of Shanghai Jiaotong University School of Medicine, Renji Hospital (Approval number KY2022-176-B)

Consent to Participate

Written, informed consent was obtained from all participants.

Consent for Publication

Not applicable.

Code Availability

Not applicable.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 279 KB)

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Ding, L., Liu, S., Yan, H. et al. Pharmacokinetics of Henagliflozin in Dialysis Patients with Diabetes. Clin Pharmacokinet 62, 1581–1587 (2023). https://doi.org/10.1007/s40262-023-01300-z

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  • DOI: https://doi.org/10.1007/s40262-023-01300-z

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