Pharmacodynamic and pharmacokinetic interactions between common antiepileptic drugs and acetone, the chief anticonvulsant ketone body elevated in the ketogenic diet in mice.
Level 5 - mechanism / opinion, no new human data
Preclinical animal interventional study
PubMed 19178560 · doi:10.1111/j.1528-1167.2008.01864.x
What was done
Mice were given subthreshold intraperitoneal doses of acetone (5 or 7.5 mmol/kg) in combination with common antiepileptic drugs (carbamazepine, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, topiramate, or valproate) and evaluated in the maximal electroshock-induced seizure model. Motor performance and long-term memory were evaluated using the chimney test and passive avoidance task, respectively. Pharmacokinetic interactions were examined by measuring total brain tissue concentrations of the antiepileptic drugs and free acetone concentrations in the brain.
What was found
Acetone (5 or 7.5 mmol/kg) enhanced the anticonvulsant activity of carbamazepine, lamotrigine, phenobarbital, and valproate against maximal electroshock seizures, while the effects of oxcarbazepine, phenytoin, and topiramate remained unchanged. Acetone (7.5 mmol/kg) did not worsen acute adverse motor or memory effects of any tested antiepileptic drug, nor did it alter brain concentrations of the antiepileptic drugs. However, valproate, carbamazepine, lamotrigine, oxcarbazepine, and topiramate significantly decreased free acetone concentrations in brain tissue, whereas phenobarbital and phenytoin had no effect. Specific numerical values, confidence intervals, and p-values were not reported in the abstract.
Why it matters
These findings indicate that acetone, a major ketone body generated during ketogenic diet therapy, can selectively potentiate the anticonvulsant efficacy of specific antiepileptic drugs without aggravating acute neurotoxicity or altering brain drug levels in mice.
Limits
The study was conducted exclusively in an acute electroshock mouse model, which may not translate directly to human pharmacokinetics or chronic epileptic syndromes. The abstract does not report the sample size, numerical seizure thresholds, or exact drug concentrations.
Cited by
- supports Acetone has anticonvulsant properties and contributes to seizure control.