Valproate
Valproate. GABA-mimetic — raises CNS GABA via GABA-T inhibition; also blocks voltage-gated Na+ channels and modulates Ca²⁺. Broad-spectrum… Oral half-life 16 h.
GABA-mimetic — raises CNS GABA via GABA-T inhibition; also blocks voltage-gated Na+ channels and modulates Ca²⁺. Broad-spectrum antiseizure + bipolar + migraine prophylaxis. Strong CYP2C9 inhibitor + UGT inhibitor (raises lamotrigine 2×). Teratogenic (NTDs); mitochondrial toxicity in young children.
PK: purest zero-content in its group — the cited paper states none of the four values, and the two numerals that superficially match belong to the OTHER drug in that interaction study. The stored 14 h was its phrase "after 14 DAYS of zonisamide treatment", a dosing duration read as a half-life. Re-sourced to Hussein 1993 (PMID:8218957), 16 healthy men given 1000 mg intravenously: "an average terminal-phase half-life of 15.9 h" and terminal volumes of "14.2-15.1 l", the lower stated endpoint being carried. THE STORED 9 L WAS BELOW EVERY INTRAVENOUS-MEASURED ADULT VALUE, and 9 appears in the literature as the UNBOUND FRACTION IN PERCENT at 45 mg/L — the same collision shape again. F 1 is now sourced: absolute bioavailability of the delayed-release form is "approximately 100%". BINDING IS SATURABLE, unbound fraction moving from 15% to 9% across the therapeutic range, so total-drug volume is itself concentration-dependent and a single value is an approximation. DEPOT TRAP LOGGED: the extended-release form has F 0.896 and releases at a CONSTANT ZERO-ORDER RATE over about 22 h, so an ER route must never inherit this row absorption or bioavailability.
Pharmacokinetics
- Oral — t½ 15.9 h · F 100% · Vd 14.2 L
- IV — t½ 15.9 h · F 100% · Vd 14.2 L
Related compounds
- Lamotrigine — major
- Phenytoin — warn
Sources: PMID:6430316, PMID:8218957, PMID:12576164, PMID:15199078