Saxagliptin
Saxagliptin. DPP-4 inhibitor — raises endogenous GLP-1 + GIP, promoting glucose-dependent insulin release. CYP3A4/5 substrate. Modest A1c… Oral half-life 3 h.
DPP-4 inhibitor — raises endogenous GLP-1 + GIP, promoting glucose-dependent insulin release. CYP3A4/5 substrate. Modest A1c reduction (~0.5%); slight heart failure signal vs sitagliptin.
PK: ITS CITATION CARRIED A PEAK TIME AND EXCRETION FRACTIONS AND NOTHING ELSE. F 0.67 appears in no abstract; the nearest figure in its own refs[] is "good bioavailability (50-75%) in the species tested" — RATS, DOGS AND MONKEYS — and 0.67 is not even that range midpoint. The human measurement is verbatim and unambiguous, from an intravenous microdose given alongside the therapeutic oral dose: "The geometric mean point estimates (90% confidence interval) F(p.o) . values for saxagliptin and dapagliflozin were 50% (48, 53%)". THIS IS THE ONE RECORD IN THIS BATCH WHERE FIXING F ALONE MAKES IT BETTER, and the direction was checked before acting: exposure moves from 23% high to 8% low, so the volume is deliberately left alone. The half-life was verbatim but hung on the wrong paper — "The elimination half-lives (t(1/2)) for saxagliptin and 5-hydroxy saxagliptin were approximately 3 and 4 hours" — and the record correctly took the parent value rather than the metabolite. ka 3.5 is unsourced but is NOT a back-derivation. THE ACTIVE METABOLITE IS UNMODELLED AND THE GAP IS QUANTIFIABLE: it runs two to three times the parent exposure at half the potency, so real DPP-4 inhibition is about 2.25 times what a parent-only occupancy row computes.
Pharmacokinetics
- Oral — t½ 3 h · F 50% · ka 3.5 h⁻¹ · Vd 151 L
Sources: PMID:22496391, PMID:22475049, PMID:19251818, PMID:22823746, PMID:22668067