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Objectives <p>Food intake affects pharmacokinetic (PK) parameters of empagliflozin (EMPA). In the treatment of chronic kidney disease, EMPA in combination with renin-angiotensin-aldosterone system (RAAS) inhibitors is widely used. This study aims to investigate how a high-fat diet (HFD) affects the PK parameters, pharmacodynamic (PD) parameters related to renal function, and PD parameters related to RAAS of EMPA.</p> Methods <p>Based on a bioequivalence study of healthy Chinese adults, twenty blood sampling points were set up for each participant before EMPA and within 48 hours after 10 mg EMPA administration to measure their plasma concentrations, and then calculate their maximum plasma concentration (C<sub>max</sub>) and area under the time-concentration curve (AUC<sub>0~t</sub>). Urine and blood glucose, uric acid, blood urea nitrogen, serum creatinine, insulin, urine β2-microglobulin (β2-MG) and α1-MG, plasma renin concentration (PRC), angiotensin II, and aldosterone levels were tested.</p> Results <p>The 90% confidence intervals of the geometric mean ratios of the fasting C<sub>max</sub> and AUC<sub>0~t</sub> for the fed group were (152.29~178.77)% and (127.21~147.29)%, not within the bioequivalence range (80.00%~125.00%). When after taking EMPA compared to before taking EMPA, urine glucoses elevated significantly (fasting: (70.9 ± 29.9) mmol/L vs (0.3 ± 0.2) mmol/L: <i>p</i> &lt; 0.001. fed: (89.6 ± 35.4) mmol/L vs (0.3 ± 0.3) mmol/L: <i>p</i> &lt; 0.001), but β2-MG levels decreased significantly (fasting: (0.080 ± 0.065) mg/L vs (0.148 ± 0.054) mg/L: <i>p</i> &lt; 0.05. fed: (0.094 ± 0.059) mg/L vs (0.145 ± 0.075) mg/L: <i>p</i> &lt; 0.05). After taking EMPA, the elevated urine glucose and decreased β2-MG level exceeded the normal ranges (urine glucose: ˂ 2.8 mmol/24 h. β2-MG: 0.1 ~ 0.3 mg/L). Fasting administration of EMPA increased PRC (<i>p</i> &lt; 0.05) but had no effect on aldosterone levels. Other parameters before and after EMPA administration in both groups had no significant difference and were all within the normal ranges.</p> Conclusions <p>The potential effects of long-term HFD on the PK and pharmacological actions of EMPA should be considered. Exploring the relationship between the elevated urine glucose and decreased β2-MG may have certain clinical value.</p> Clinical trial registration <p>ChiCTR2400089102, retrospectively registered in <a href="https://www.chictr.org.cn/">https://www.chictr.org.cn/</a> on 2 September 2024.</p>

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To investigate the effect of a high-fat diet on pharmacokinetics/renal function/RAAS-related parameters after a single dose of empagliflozin in healthy Chinese adults

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  • 发表日期：

    2026年2月9日

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  • Yi Jin,
  • Wenyan Zhao,
  • Qian Li,
  • Sunqi Ding,
  • Shuangshuang Tian,
  • Zhaodi Han,
  • Hui Wu,
  • Lu Bai,
  • Hui Liao

摘要

Objectives

Food intake affects pharmacokinetic (PK) parameters of empagliflozin (EMPA). In the treatment of chronic kidney disease, EMPA in combination with renin-angiotensin-aldosterone system (RAAS) inhibitors is widely used. This study aims to investigate how a high-fat diet (HFD) affects the PK parameters, pharmacodynamic (PD) parameters related to renal function, and PD parameters related to RAAS of EMPA.

Methods

Based on a bioequivalence study of healthy Chinese adults, twenty blood sampling points were set up for each participant before EMPA and within 48 hours after 10 mg EMPA administration to measure their plasma concentrations, and then calculate their maximum plasma concentration (Cmax) and area under the time-concentration curve (AUC0~t). Urine and blood glucose, uric acid, blood urea nitrogen, serum creatinine, insulin, urine β2-microglobulin (β2-MG) and α1-MG, plasma renin concentration (PRC), angiotensin II, and aldosterone levels were tested.

Results

The 90% confidence intervals of the geometric mean ratios of the fasting Cmax and AUC0~t for the fed group were (152.29~178.77)% and (127.21~147.29)%, not within the bioequivalence range (80.00%~125.00%). When after taking EMPA compared to before taking EMPA, urine glucoses elevated significantly (fasting: (70.9 ± 29.9) mmol/L vs (0.3 ± 0.2) mmol/L: p < 0.001. fed: (89.6 ± 35.4) mmol/L vs (0.3 ± 0.3) mmol/L: p < 0.001), but β2-MG levels decreased significantly (fasting: (0.080 ± 0.065) mg/L vs (0.148 ± 0.054) mg/L: p < 0.05. fed: (0.094 ± 0.059) mg/L vs (0.145 ± 0.075) mg/L: p < 0.05). After taking EMPA, the elevated urine glucose and decreased β2-MG level exceeded the normal ranges (urine glucose: ˂ 2.8 mmol/24 h. β2-MG: 0.1 ~ 0.3 mg/L). Fasting administration of EMPA increased PRC (p < 0.05) but had no effect on aldosterone levels. Other parameters before and after EMPA administration in both groups had no significant difference and were all within the normal ranges.

Conclusions

The potential effects of long-term HFD on the PK and pharmacological actions of EMPA should be considered. Exploring the relationship between the elevated urine glucose and decreased β2-MG may have certain clinical value.

Clinical trial registration

ChiCTR2400089102, retrospectively registered in https://www.chictr.org.cn/ on 2 September 2024.