Dichloroacetate
Dichloroacetate. Small organic acid that inhibits pyruvate dehydrogenase kinase (PDK1–4), locking pyruvate dehydrogenase (PDH) in its active… Oral half-life 3.4 h.
Small organic acid that inhibits pyruvate dehydrogenase kinase (PDK1–4), locking pyruvate dehydrogenase (PDH) in its active, dephosphorylated form. Shifts metabolism from glycolysis / lactate production toward mitochondrial oxidative phosphorylation — lowers circulating lactate and, in cancer cells exhibiting the Warburg effect, restores apoptotic competence by repolarising mitochondria. Metabolised by glutathione-transferase-zeta-1 (GSTZ1); DCA itself inactivates GSTZ1, so terminal t½ lengthens dramatically with chronic dosing (from ~1 h initially to 10+ h after weeks). Dose-limiting toxicity: reversible peripheral neuropathy.
PK re-sourced to Krishna 1996 (PMID:8824690), 11 adults, verbatim "V = 0.44(0.2) 1 kg-1" (31 L at 70 kg) and "t1/2 = 3.4(2.2) h" — one paper for both. The previous citation states none of the four values; its only bioavailability figure is a range, "ranging from 27 to 100%", of which the stored F of 1 was the upper end. THE CRITICAL CAVEAT: dichloroacetate INHIBITS ITS OWN METABOLISM, so no single half-life is defensible — the first dose gives 1.58 h, later doses 3.64 h and then 9.9 h, with washout taking from one week to over three months (PMID:1878534). This record models a single dose only and will understate exposure on any repeated-dosing simulation. ka 2.5 /h dropped as unstated. SALT FORM: DADA (diisopropylamine dichloroacetate) contains dichloroacetate, but its counterion and mass differ from sodium dichloroacetate; this record does not convert DADA doses or characterize the diisopropylamine moiety (PMID:10545828). Separate salt-specific entry: dada; no PK or dose conversion is inherited between these records.
Pharmacokinetics
- Oral — t½ 3.4 h · F 100% · Vd 31 L
- IV — t½ 3.4 h · F 100% · Vd 31 L
Sources: PMID:2554095, PMID:8824690, PMID:1878534