Sitagliptin
Sitagliptin. Competitive, reversible DPP-4 (dipeptidyl peptidase-4) inhibitor — blocks degradation of the endogenous incretins GLP-1 and GIP… Oral half-life 7.4 h.
Competitive, reversible DPP-4 (dipeptidyl peptidase-4) inhibitor — blocks degradation of the endogenous incretins GLP-1 and GIP, raising their plasma levels 2–3× and potentiating glucose-dependent insulin release plus glucagon suppression. Weight-neutral, low hypoglycaemia risk (glucose-dependent action). CV-neutral (TECOS trial).
PK: THE FEASIBILITY TEST NAMES THE GUILTY PARAMETER, AND IT IS NOT THE VOLUME. Three independent routes agree the record over-predicts exposure 1.91x — a bioavailability-corrected clearance of 28.69 L/h, a renal clearance route giving 29.1, and a verbatim exposure giving 27.6, against a stored 15.02. The obvious repair is to raise the volume, and THE Cmax-OVER-AUC IDENTITY FORBIDS IT: the verbatim quartet "AUC(0-inf) (3,621 +/- 222.5 ... ng h/ml)... C(max) (282.9 +/- 7.7 ... ng/ml)... t(1/2) (7.4 +/- 0.6 ... h)" gives an exposure-to-peak ratio of 12.80 h, which passes the floor at a 7.4 h half-life and FAILS IT at the stored 10.4 — so raising the volume would fix exposure and destroy the peak. The half-life moves instead, to a verbatim value, and the volume follows from a verbatim clearance at that half-life. The stored bioavailability is verbatim in a paper with a real intravenous arm and is untouched, which also acquits class 6. A SPECULATION IS RECORDED AS UNPROVEN: the only near-10 h sitagliptin half-life indexed is the GEMFIBROZIL-INHIBITED ARM of the very study now cited, whose control is 7.4 — the same control-versus-treated confusion found on pioglitazone — but 10.4 is not 10.0, so the path is not established.
Pharmacokinetics
- Oral — t½ 7.4 h · F 87% · Vd 266 L
Related compounds
- Metformin — synergistic
- Semaglutide / GLP-1 RAs — caution
Sources: PMID:17220239, PMID:15634008, PMID:22173280, PMID:17575559