Pharmacokinetics and Dialyzability of Dapagliflozin in Dialysis Patients
Status:
Recruiting
Trial end date:
2022-08-01
Target enrollment:
Participant gender:
Summary
Sodium-glucose co-transporter 2 inhibitors (Sglt2i) attenuate the incidence of cardiovascular
events in individuals with preserved or mildly reduced kidney function. Whether this benefit
is also observed among individuals with end-stage renal disease (ESRD), in whom
cardiovascular disease is a leading cause of mortality, remains unexplored. To appraise the
influence of dialysis on the pharmacokinetics of Sglt2i is a prerequisite to determining the
treatment regimen that best fits this population.
In this study ESRD individuals, aged 18 years and older, on a regular dialysis regimen for a
minimum of 3 months at the Nephrology Division of the Clinics Hospital of the University of
Campinas (Unicamp) will be enrolled in a pharmacokinetics study.
In the single-dose protocol, hemodialysis participants will take Dapagliflozin 10mg P.O.
immediately before the dialysis session, and blood samples will be collected every 30min
during dialysis and again 24h and 48h after termination. The dialysate will be continuously
sampled in a tank and aliquots collected for further analysis.
In the multiple-dose protocol, both hemodialysis and peritoneal dialysis participants will
take Dapagliflozin 10mg P.O. daily in the morning for 7 days. Blood samples will be collected
at baseline, and again after 48h and 7 days.
The plasma levels of dapagliflozin and its inactive metabolite, D3OG, will be calculated from
blood and dialysate samples using liquid chromatography mass spectrometry.
The primary outcome is the plasma concentration-time curve of dapagliflozin and its inactive
metabolite D3OG during a regular hemodialysis session. Secondary outcomes are: (i) the
steady-state plasma concentration of Dapa; (ii) the accumulation ratio of Dapa; (iii) the
total mass of Dapa and D3OG extracted by the dialysate; (iv) the dialytic clearance of
dapagliflozin.