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 min ) of the steady state on Day 10, and single hemodialysis clearance of henagliflozin were measured. Results The mean values of C max 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 inf 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 max values ranged from 1 to 3 h across the dose range. The mean values of T 1/2 of henagliflozin were 14.1–14.5 and 16.2–21.0 h in the 5 mg and 10 mg groups, respectively. The C min 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.