Pharmacodynamic and pharmacokinetic interactions between common antiepileptic drugs and acetone, the chief anticonvulsant ketone body elevated in the ketogenic diet in mice
Version of Record online: 24 OCT 2008
Wiley Periodicals, Inc. © 2008 International League Against Epilepsy
Volume 50, Issue 5, pages 1132–1140, May 2009
How to Cite
Zarnowska, I., Luszczki, J. J., Zarnowski, T., Buszewicz, G., Madro, R., Czuczwar, S. J. and Gasior, M. (2009), Pharmacodynamic and pharmacokinetic interactions between common antiepileptic drugs and acetone, the chief anticonvulsant ketone body elevated in the ketogenic diet in mice. Epilepsia, 50: 1132–1140. doi: 10.1111/j.1528-1167.2008.01864.x
- Issue online: 7 MAY 2009
- Version of Record online: 24 OCT 2008
- Accepted August 13, 2008; Early View publication October 24, 2008.
- Ketogenic diet;
- Antiepileptic drugs
Purpose: Acetone is the principal ketone body elevated in the ketogenic diet (KD), with demonstrated robust anticonvulsant properties across a variety of seizure tests and models of epilepsy. Because the majority of patients continue to receive antiepileptic drugs (AEDs) during KD treatment, interactions between acetone and AEDs may have important clinical implications. Therefore, we investigated whether acetone could affect the anticonvulsant activity and pharmacokinetic properties of several AEDs against maximal electroshock (MES)–induced seizures in mice.
Methods: Effects of acetone given in subthreshold doses were tested on the anticonvulsant effects of carbamazepine (CBZ), lamotrigine (LTG), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), topiramate (TPM) and valproate (VPA) against MES-induced seizures in mice. In addition, acute adverse effects of acetone–AEDs combinations were assessed in the chimney test (motor performance) and passive avoidance task (long-term memory). Pharmacokinetic interactions between acetone and AEDs were also studied in the mouse brain tissue.
Results: Acetone (5 or 7.5 mmol/kg, intraperitoneally [i.p.]) enhanced the anticonvulsant activity of CBZ, LTG, PB, and VPA against MES-induced seizures; effects of OXC, PHT, and TPM were not changed. Acetone (7.5 mmol/kg) did not enhance the acute adverse-effect profiles of the studied AEDs. Acetone (5 or 7.5 mmol/kg, i.p.) did not affect total brain concentrations of the studied AEDs. In contrast, VPA, CBZ, LTG, OXC, and TPM significantly decreased the concentration of free acetone in the brain; PB and PHT had no effect.
Conclusions: Acetone enhances the anticonvulsant effects of several AEDs such as VPA, CBZ, LTG, and PB without affecting their pharmacokinetic and side-effect profiles.