Rimegepant
Rimegepant. Small-molecule CGRP receptor antagonist — competitive blockade at the CLR/RAMP1 receptor. Approved for both acute migraine treatment… Oral half-life 11 h.
Small-molecule CGRP receptor antagonist — competitive blockade at the CLR/RAMP1 receptor. Approved for both acute migraine treatment and migraine prevention (every-other-day dosing). No vasoconstriction → safe in CAD where triptans are contraindicated. CYP3A4 substrate.
PK: TWO FORMAL DEFECTS THAT CANCEL TO WITHIN 4% OF A REAL MEASUREMENT — DO NOT FIX EITHER. The stored volume is COMPUTED, the sum of a published apparent central and peripheral volume, and the stored bioavailability is an uncited label figure; the paper own wording confirms both are apparent. And yet, against a dose- AND FORMULATION-matched study of the same 75 mg orally disintegrating tablet — "mean values were 937 ng/mL (maximum concentration), 4582 h*ng/mL (area under the concentration-time curve, 0 to infinity), 7.7 hours (terminal elimination half-life), and 19.9 L/h (apparent clearance)" — this record reproduces exposure at +3.9%. PINNING F TO 1, THE APPARENT CLASS-6 FIX, MAKES IT +62%; ADOPTING THE VERBATIM 7.7 h HALF-LIFE ALONE MAKES IT -27%. The absorption rate is verbatim from a population fit, with the caveat that it belongs to a model whose four transit compartments carry the delay, so lifting it alone discards that structure. A residual is recorded as irreducible: the peak is under-predicted about threefold because the central volume is 2.4 times smaller than the steady-state volume and one compartment cannot hold both. My formulation question is answered — the cited model IS orally-disintegrating-tablet-inclusive; the record SECOND reference is the capsule free-base study and its half-life range is not the source of the stored value.
Pharmacokinetics
- Oral — t½ 11 h · F 64% · ka 3.86 h⁻¹ · Vd 160 L
Sources: PMID:40614133, PMID:37282507, PMID:36808268