Pharmacokinetics of Henagliflozin in Dialysis Patients with Diabetes.

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 (C) of the steady state on Day 10, and single hemodialysis clearance of henagliflozin were measured.

Results: The mean values of C 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 AUC were 777-811 h*ng/mL and 1290-1730 h*ng/mL in the 5 mg and 10 mg henagliflozin groups, respectively. The median T values ranged from 1 to 3 h across the dose range. The mean values of T of henagliflozin were 14.1-14.5 and 16.2-21.0 h in the 5 mg and 10 mg groups, respectively. The C 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.