Topiramate
Topiramate. Multi-target antiseizure — blocks Na+ + Ca²⁺ channels, enhances GABA-A, antagonizes AMPA / kainate, weak carbonic anhydrase… Oral half-life 22 h.
Multi-target antiseizure — blocks Na+ + Ca²⁺ channels, enhances GABA-A, antagonizes AMPA / kainate, weak carbonic anhydrase inhibition. Migraine prophylaxis + weight-loss combination (Qsymia). Cognitive slowing, paresthesias, kidney stones (CA inhibition).
PK: THE FURTHEST A DIGIT COLLISION HAS TRAVELLED. The stored 21 h had no half-life behind it — the only 21 in the cited abstract is "21 days of washout between treatments", a study-design interval. That paper states four half-lives, 55.7, 80.2, 72.5 and 37.1 h, none of them 21, and it is an EXTENDED-RELEASE study cited for an immediate-release row; its F of 91.2% is relative to Topamax, not absolute. Re-sourced to the first-in-human phase I (PMID:8930774), verbatim "Elimination half-life (t1/2) values calculated from plasma (21.5 hrs)" and "volume of distribution (Vd/F) was 38.5 to 58.0 L" — the stated lower endpoint is stored and F is pinned to 1 because that volume is APPARENT. MONOTHERAPY ONLY: oral and non-renal clearance run two- to three-fold higher with enzyme-inducing antiepileptics (PMID:8764818). ka 1.5 /h dropped.
Pharmacokinetics
- Oral — t½ 21.5 h · F 100% · Vd 38.5 L
Sources: PMID:10768298, PMID:8930774, PMID:8764818, PMID:19764603