Canagliflozin
Canagliflozin. Selective inhibitor of renal proximal-tubule SGLT2 (~90% of filtered glucose reabsorption) with mild SGLT1 activity (intestinal —… Oral half-life 12 h.
Selective inhibitor of renal proximal-tubule SGLT2 (~90% of filtered glucose reabsorption) with mild SGLT1 activity (intestinal — contributes to post-prandial glucose flattening). Induces urinary glucose excretion (~80–100 g/day at 300 mg) → lower plasma glucose, modest weight loss (~2–3 kg), mild blood-pressure reduction via osmotic diuresis. CV and renal benefits in T2DM (CANVAS, CREDENCE) at least partially independent of glycaemic effect.
PK: THE BEST RECORD OF ITS GROUP, AND THE CROSS-DRUG TRANSPLANT SCREEN COMES BACK NEGATIVE. F 0.65 and V 119 L are both verbatim from an oral-plus-intravenous-microdose study — "The absolute oral bioavailability of canagliflozin was 65%" and "Vdss 83.5 (29.2) L, Vdz 119 (41.6) L" — the volume intravenous-derived, so the pairing is right. THE DANGEROUS NEAR-MISS IS RECORDED SO IT IS NOT "FIXED" LATER: dapagliflozin stores V 112 L and its published volume is about 118, within one unit of this record 119 — but 119 is verbatim this drug own intravenous value in its own study. Coincidence, not transplant, and the empagliflozin-dapagliflozin pair found in the previous batch stays isolated. The half-life was truncated from its own paper "t1/2 11.6 (0.70) hours". ka 1.2 appears nowhere, and this record own population reference gives the reason it should not be re-sourced rather than replaced: absorption is "sequential zero- and first-order absorption" with a lag, so a bare first-order rate is the wrong model class.
Pharmacokinetics
- Oral — t½ 11.6 h · F 65% · Vd 119 L
Sources: PMID:26293616, PMID:27136910, PMID:27189972