Lamotrigine
Lamotrigine. Voltage-gated sodium-channel blocker — also weak Ca²⁺-channel + glutamate-release modulation. First-line for focal epilepsy +… Oral half-life 28 h.
Voltage-gated sodium-channel blocker — also weak Ca²⁺-channel + glutamate-release modulation. First-line for focal epilepsy + bipolar maintenance (mood stabilizer). UGT1A4 substrate (valproate doubles half-life). SJS/TEN risk → mandatory 6-week titration.
PK: THE VOLUME WAS RIGHT AND ITS HOME WAS A DIFFERENT PAPER - "The final population estimate of V/F was 77.4 l with an interpatient variability of 34%", from 163 patients on MONOTHERAPY, which also answers the background-regimen question this drug always raises. A TRAP IS RECORDED SO NOBODY RE-SOURCES IT: another abstract reports an "apparent volume of distribution: 1.08 +/- 0.37 l/kg" that also scales to about 77 L, but its ANALYTE IS CARBAMAZEPINE-10,11-EPOXIDE. Because 77.4 is explicitly V/F, F is pinned to 1, and the half-life becomes the value coherent with that same study measured clearance, "CLo increased by 17.3% during the 48 weeks of therapy, from 1.94 to 2.28 l h(-1)" - the stored 36 h would assert 1.49 L/h and over-predict exposure by 1.3 to 1.5 times. The derivation is disclosed. THE INTERACTION CAVEAT IS THE POINT OF THIS RECORD and is now declared: enzyme inducers "reduce the half-life of lamotrigine (to mean values of 13.5 to 15 hours), whereas valproic acid increases the half-life ... (to mean values of 48.3 to 59 hours)", a fourfold span, so every stored value here means MONOTHERAPY. COUNTER-EVIDENCE ON F: lamotrigine DOES have an intravenous form, and the primary absolute study gives "73% and 92%" for immediate- and extended-release, against the 98% everyone quotes. PK: THE STORED ABSORPTION RATE WAS THE SOLVER DEFAULT WEARING A CITATION. A ka of 1.0/h is exactly what resolvePk substitutes when the field is ABSENT, and no source on this record states one. Removing it is NUMERICALLY A NO-OP — the resolver supplies the identical number — so no curve moves; what changes is that the record stops asserting an absorption rate it never measured. This is the same shape already found on a volume of 35 L, which is likewise the default at the seventy-kilogram reference. THE WIDER DEBT IS LEFT ALONE ON PURPOSE: twelve values account for 152 of the 276 authored absorption rates, but the other eleven are NOT the default, so deleting those would move their curves rather than leave them, which is the error this audit spent a batch documenting.
Pharmacokinetics
- Oral — t½ 27.7 h · F 100% · Vd 77.4 L
Sources: PMID:8119045, PMID:9429124, PMID:9159559, PMID:25903807