Linagliptin
Linagliptin. Highly selective, tight-binding DPP-4 inhibitor — prevents inactivation of endogenous GLP-1 and GIP → enhanced glucose-dependent… Oral half-life 12 h.
Highly selective, tight-binding DPP-4 inhibitor — prevents inactivation of endogenous GLP-1 and GIP → enhanced glucose-dependent insulin release and suppressed glucagon. Unique among DPP-4 inhibitors in being eliminated primarily unchanged via bile/feces (<5% renal) with a non-linear PK driven by saturable DPP-4 target binding — effective t½ ~12 h despite terminal t½ of 100+ h due to target-mediated disposition.
PK: THIS RECORD HAD NO VOLUME AT ALL, AND THE SOLVER SUPPLIED ONE SILENTLY. resolvePk substitutes 0.5 L/kg for a missing V_L, so linagliptin was rendering at 35 L and therefore 10.4x high on exposure — against a verbatim "geometric mean area under the plasma concentration-time curve (AUC) was 71 ng x h ml-1" it asserted 742, and against a verbatim "Cmax after single dose was 4.9 ng/ml" it asserted 38.7. The value now stored is verbatim from a paper that was not in refs[]: "The model-derived estimates of the V(ss) and clearance of linagliptin not bound to DPP-4 were 402.2 L and 26.9 L/h". Exposure lands within nine percent, and the two numbers cross-check — their ratio gives a 10.4 h half-life, matching the accumulation half-life this record already stores. CLASS 6 IS ACQUITTED because that volume comes from intravenous dosing. AND MY PRIOR ABOUT THE HALF-LIFE WAS WRONG IN THE OPPOSITE DIRECTION TO ESLICARBAZEPINE: I expected the stored 12 h to be an effective half-life masquerading as an elimination one, but here that is the CORRECT choice — the 126-139 h terminal phase is target-binding-driven and carries almost no exposure, and storing it would make exposure 10.5x too high. A CAVEAT IS LOGGED: clearance and volume both rise with dose, so this is defensible at the fixed stored dose and not across doses.
Pharmacokinetics
- Oral — t½ 12 h · F 30% · ka 2.12 h⁻¹ · Vd 402.2 L
Sources: PMID:22568694, PMID:18223196, PMID:23073142, PMID:21053992