Perampanel
Perampanel. Selective non-competitive AMPA glutamate receptor antagonist — first-in-class. Adjunct for partial-onset + primary generalized… Oral half-life 4.5 d.
Selective non-competitive AMPA glutamate receptor antagonist — first-in-class. Adjunct for partial-onset + primary generalized tonic-clonic seizures. Black-box for psychiatric / behavioral adverse effects (aggression, suicidality).
PK: half-life re-cited and corrected 105 -> 109 h. The stored 105 h was verbatim but sat in the OBJECTIVES of its paper as borrowed background ("In vitro studies and Phase I trials indicate"), not as that study measurement; Jing 2023 (PMID:36746851) measures it, verbatim "mean t1/2, 109 h" at steady state. V 77 L is the approval-document figure and appears in no abstract; replaced by 64.35 L from a population fit (PMID:39902756) with F pinned to 1, since that volume is apparent. Bioavailability near unity is supported by an oral-to-intravenous exposure ratio of "1.03 (0.97-1.09)" (PMID:35596529). ka 1.0 /h dropped as unstated. PK: ABSORPTION RATE AUTHORED FROM A VERBATIM PEAK TIME. This row carried no ka, so the solver substituted 1.0/h and the modelled peak landed at 5.1 h — for a slowly-absorbed oral product that is wrong by design, not by a little. Source: "concentration (tmax) was 0.75-1.0 h". THIS RECORD IS THE ONE WHOSE DEFAULT IS TOO SLOW rather than too fast — 5.1 h against a published sub-hour peak — so the under-correcting endpoint is the LONGER one, 1.0 h. 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 7.012/h, which reproduces 1 h on substitution. EXPOSURE IS UNCHANGED: the absorption rate cancels out of AUC entirely, so only the shape moves.
Pharmacokinetics
- Oral — t½ 4.5 d · F 100% · ka 7.012 h⁻¹ · Vd 64.35 L
Sources: PMID:28535410, PMID:36746851, PMID:35596529, PMID:39902756