Pharmacokinetic Properties of Dapagliflozin in Hemodialysis and Peritoneal Dialysis Patients.

Background Sodium-glucose cotransporter 2 inhibitors (SGLT2i) attenuate incident cardiovascular outcomes irrespective of baseline glomerular filtration rate in conservatively managed chronic kidney disease. As this condition inexorably progresses to demanding kidney replacement therapy drug withdrawal is supported by the current lack of evidence of safety of SGLT2i in dialysis. Methods This study was a prospective, single-center, open-label trial ClinicalTrials.gov Identifier: NCT05343078) aimed at assessing the pharmacokinetic and safety of dapagliflozin in kidney failure individuals on regular dialysis regimens compared to type 2 diabetes, age- and gender-matched controls with normal kidney function. Peripheral blood samples were collected from both groups every 30min for 4h and again after 48h following ingestion of dapagliflozin 10mg, which occurred immediately prior to dialysis session initiation in the kidney failure group. This protocol occurred in drug-naïve individuals and again following six daily doses of dapagliflozin to assess whether the drug had accumulated. The plasma and dialysate levels of dapagliflozin at each timepoint were determined by liquid chromatography and used to calculate pharmacokinetics parameters (peak concentration (Cmax) and area under the plasma-concentration vs time curve (AUC)) for each participant. Results Dapagliflozin Cmax was 117ng/mL and 97.6ng/mL in the kidney failure and control groups, respectively, whereas the corresponding accumulation ratios were 26.7% and 9.5%. No serious adverse events were reported for neither group. Dapagliflozin recovered from dialysate corresponded to 0.10% of the administered dose. Conclusions In individuals with kidney failure on dialysis, dapagliflozin was well-tolerated, slightly dialyzable, and had non-accumulating pharmacokinetic properties.