Abstract: TH-OR97
Pharmacokinetics of Henagliflozin in Dialysis Patients with Diabetes
Session Information
- Onconephrology and Precision Pharmacology
November 02, 2023 | Location: Room 107, Pennsylvania Convention Center
Abstract Time: 05:24 PM - 05:33 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Author
- Gu, Leyi, 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, Shanghai, China
Group or Team Name
- PHD Group.
Background
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are recommended to treat heart failure, irrespective of the presence of type 2 diabetes. Heart failure is one of the most common complications in dialysis patients. Not all SGLT2i are recommended for use in dialysis patients because less glucose enters the proximal tubule and the effects of inhibiting glucose and sodium reabsorption are reduced, as well as due to a lack of efficacy and safety data. However, emerging evidence has suggested that SGLT2i improve heart failure outcome through the off-target effect. Therefore, patients on dialysis with heart failure may benefit from SGLT2i. We conducted this study to evaluate the pharmacokinetics and safety of Henagliflozin doses of 5 mg and 10 mg in dialysis patients with diabetes.
Methods
In this prospective, randomized, open-label study, 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. Plasma concentrations of Henagliflozin were analyzed by using validated liquid chromatography-tandem mass spectrometry method.
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.
Conclusion
Henagliflozin at the current recommended dosage may be safe although it accumulates in patients on dialysis. Clinical trials should be conducted to examine the cardioprotective effects of Henagliflozin in dialysis patients.
Funding
- Government Support – Non-U.S.