Phenytoin
Phenytoin. Use-dependent Na⁺ channel blocker — stabilises inactivated state → prevents high-frequency neuronal firing characteristic of seizure. Saturable metabolism…
Use-dependent Na⁺ channel blocker — stabilises inactivated state → prevents high-frequency neuronal firing characteristic of seizure. Saturable metabolism (Michaelis-Menten) → small dose increases cause disproportionate level rises. CYP inducer + substrate.
PK: the Michaelis constant 4.03 mg/L is verbatim and stands, but it is the CYP2C9 *1/*1 SUBGROUP value — the same abstract gives 5.96 for *1/*3 — so storing it unqualified silently asserts a genotype. The maximum rate is corrected: 0.53 appears nowhere, the paper states "Vmax=22.66.(BWT/60.96)0.454(mg/h)", an AMOUNT rate, and 22.66 mg/h over the 50 L reference volume gives 0.453. That volume and that rate now travel as a declared pair; neither is independently sourced, and 50 L itself collides with the abstract "additional 50 patients". THE FIXED HALF-LIFE IS REMOVED: with these parameters the apparent half-life is about 25 h at 15 mg/L and 9 h at 5 mg/L, so a stored 19 h was a first-order leftover contradicting the record own saturable model. It was in any case inert, since the solver ignores a rate constant on a saturable route. F 0.9 IS DELETED AS A PROTEIN-BINDING PERCENTAGE — a reference on this very record says "approximately 90% bound to plasma proteins" — and an oral bioavailability is ill-defined here anyway, because exposure after a test dose varies with the background concentration. Values are TOTAL drug; free fraction rises on valproate co-therapy. Saturable elimination is a DISPOSITION property, so the Michaelis parameters are carried on both routes.
Pharmacokinetics
- Oral — Vd 50 L
- IV — F 100% · Vd 50 L
Related compounds
- Hormonal contraceptives — warn
- Atorvastatin — warn
- Quetiapine — major
- Ethinyl Estradiol — warn
Sources: PMID:383353, PMID:2126946, PMID:21635243, PMID:11199955