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
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Objectives Literature showed that a high-fat diet (HFD) has an opposite effect on the pharmacokinetic (PK) parameters of empagliflozin (EMPA). EMPA combined with renin-angiotensin-aldosterone system(RAAS)inhibitors is widely used for the treatment of chronic kidney disease. In this study, we investigated the effects of HFD on the PK of EMPA, renal function-related parameters (RF-RP), and RAAS-related parameters (RAAS-RP) affected by EMPA. Methods Based on a bioequivalence study in healthy Chinese adults, twenty blood concentration values were obtained before and within 48 h after EMPA administration in the fasting and fed groups. The maximum plasma concentration (C max ), time to reach C max (T max ), and area under the time-concentration curve (AUC) were calculated. Guided by C max and T max , urine and blood samples were collected and glucose, uric acid, blood urea nitrogen, serum creatinine, insulin, urine α1-microglobulin, β2-microglobulin, plasma renin concentration (PRC), angiotensin II, and aldosterone levels were tested. Estimated glomerular filtration rates were calculated. Results The 90% confidence intervals of the geometric mean ratios of fasting T max , C max , and AUC for the fed group were not within the bioequivalence range. After taking EMPA, urine glucose was higher but β2-microglobulin was significantly lower than before taking EMPA (four: P < 0.001) in the two groups, and both indicators exceeded the normal ranges. Fasting administration of EMPA increased PRC (P < 0.05) but had no effect on aldosterone levels. Other indicators before and after EMPA administration in both groups were within the normal ranges. Conclusions HFD affected the PK parameters of EMPA; however, no further effects on RF-RP and RAAS-RP were by EMPA. Clinical trial registration ChiCTR2400089102, retrospectively registered in https://www.chictr.org.cn/ on 2 September 2024.
