Abstract: TH-OR98
Canagliflozin Pharmacokinetics at Steady State in Patients on Maintenance Hemodialysis
Session Information
- Onconephrology and Precision Pharmacology
November 02, 2023 | Location: Room 107, Pennsylvania Convention Center
Abstract Time: 05:33 PM - 05:42 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Mavrakanas, Thomas, McGill University Health Centre, Montreal, Quebec, Canada
- Gritsas, Ari, McGill University Health Centre, Montreal, Quebec, Canada
- Tsirella, Efrosyne, McGill University Health Centre, Montreal, Quebec, Canada
- Rios, Norka, McGill University Health Centre, Montreal, Quebec, Canada
- Sharma, Abhinav, McGill University Health Centre, Montreal, Quebec, Canada
- Suri, Rita, McGill University Health Centre, Montreal, Quebec, Canada
Background
Sodium glucose co-transporter 2 (SGLT-2) inhibitors improve cardiovascular and kidney outcomes in patients with preserved renal function or with mild and moderate chronic kidney disease. However, they have not been studied in patients on maintenance hemodialysis (HD). Detailed study of SGLT-2 inhibitor pharmacokinetics in patients receiving HD is the first step to establishing their safety in this population.
Methods
Patients with kidney failure on maintenance HD for at least 3 months were invited to participate. Those with type 1 diabetes mellitus, euglycemic ketoacidosis, or liver disease were excluded. All participants received 100 mg of canagliflozin once daily for nine days. Venous blood samples were collected immediately before (0) and 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours after canagliflozin administration for pharmacokinetic analyses on day 8 (a mid-week non-dialysis day) and hourly during hemodialysis on day 9. Canagliflozin plasma levels were measured with liquid chromatography- mass spectrometry and compared to published estimates in healthy controls.
Results
We enrolled 10 patients (59 ± 14 years old, 30% female, median dialysis duration 26 months). Canagliflozin levels reached steady state on day 4, based on a calculated half-life of 7.3 hours. Pharmacokinetic results on day 8 are shown in the Table. There were no significant differences in drug exposure, peak plasma levels, nor time to peak plasma levels between our patients and patients with preserved renal function. Canagliflozin levels were not modified by hemodialysis (p=0.39).
Conclusion
Drug exposure with canagliflozin 100 mg daily is similar between patients receiving HD and individuals with preserved kidney function, and levels were not affected by HD. These results suggest canagliflozin does not accumulate in HD patients and trials of canagliflozin may be safely conducted in patients on HD to test its efficacy.
Canagliflozin pharmacokinetics in hemodialysis
| Parameter | Hemodialysis | Preserved renal function | p-value |
| AUC0-24 (ng.h/ml) | 8267 ± 4265 | 6377 ± 1285 | 0.19 |
| Cmin (ng/ml) | 87 (57-201) | - | - |
| tmax (hours) | 2.1 (1.9-3.2) | 2.0 (1.0-4.0) | 0.18 |
| Cmax (ng/ml) | 1122 ± 537 | 943 ± 239 | 0.32 |
AUC0-24, drug exposure (area under the curve between 0 and 24h); Cmin, trough level; tmax, time to peak plasma concentration; Cmax, peak plasma concentration.
Funding
- Private Foundation Support