Galcanezumab
Galcanezumab, a biologic. Humanised IgG4 mAb binding CGRP ligand with high affinity → blocks CGRP engagement of the canonical… Subcutaneous half-life 27 d.
Humanised IgG4 mAb binding CGRP ligand with high affinity → blocks CGRP engagement of the canonical trigeminovascular receptor. Only CGRP mAb with an FDA indication for episodic cluster headache. Onset within the first month; well tolerated with minimal systemic side effects.
PK: Kielbasa 2020 (PMID:31482569), population analysis pooling seven studies of healthy individuals and migraine patients, verbatim "the apparent volume of distribution was 7.33 L (34% IIV)" and "half-life was 27 days", from a one-compartment model with linear elimination. The half-life stands as stored. F is pinned to 1 BECAUSE that volume is APPARENT (V/F) and already contains bioavailability. The stored F of 0.59 is deleted outright: it appears nowhere — not in the cited paper, not in the approval document, not in the literature — and every published galcanezumab parameter is apparent precisely because no study has ever included an IV arm, which is also why an absolute F cannot exist for it. Pairing that invented number with an apparent volume understated exposure by roughly 40%. mw corrected from the generic 148000 to 147000; note this is an IgG4, so a generic IgG1 mass was wrong on isotype as well as on number. An independent first-in-human estimate puts V/F at 11.2 L (PMID:33740315); not averaged. PK: ABSORPTION RATE AUTHORED FROM THE EMGALITY LABEL. This row carried no ka, so the solver substituted 1.0/h and put the peak at 6.8 h. Source, verbatim from the current FDA label (DailyMed setid 33a147be-233a-40e8-a55e-e40936e28db0): "Following a subcutaneous dose of galcanezumab-gnlm, the time to maximum concentration was about 5 days." Stated twice in the label, the second time alongside "the elimination half-life is 27 days", which matches the stored value exactly. PUBMED HAS THIS NOWHERE — 27 targeted searches across two passes returned four usable peak times for this whole class, because Tmax is a label figure that rarely reaches an abstract. A regulatory label is already a first-class source in this schema. With the stored half-life fixing ke, Tmax solves uniquely for ka by inverting the model own definition, ln(ka/ke)/(ka-ke) = Tmax — ARITHMETIC, NOT AN ESTIMATE — giving 0.02839/h, which reproduces 120 h on substitution. EXPOSURE IS UNCHANGED: the absorption rate cancels out of AUC, so only the shape moves.
Pharmacokinetics
- Subcutaneous — t½ 27.0 d · F 100% · ka 0.02839 h⁻¹ · Vd 7.33 L
Sources: PMID:31482569, PMID:33740315