Canagliflozin Pharmacokinetics at Steady State in Patients on Maintenance Hemodialysis
Bibliographic record
Abstract
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). Conclusions: 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. Funding: Private Foundation Support 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".