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Pharmacodynamic Interactions Between Phenytoin and Valproate
- Source :
- Clinical Neuropharmacology. 17:32-37
- Publication Year :
- 1994
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 1994.
-
Abstract
- Although the current trend is to use monotherapy in the treatment of epilepsy, combination therapy is still employed in patients who have failed to respond to monotherapy. There is little clinical or experimental documentation of evidence against or in favor of anticonvulsant combination therapy. In this context, anticonvulsant and neurotoxic pharmacodynamic interactions between phenytoin (PHT) and valproate (VPA) were assessed in an experimental model in mice. All results were expressed in terms of brain drug concentrations for eliminating any pharmacokinetic interaction from the analysis. Both the median neurotoxic and the median anticonvulsant brain concentrations were determined for each drug used alone and for the combination. The interaction for the combination of PHT and VPA was shown to be supraadditive for the anticonvulsant activity, indicating an antiepileptic potentiation, whereas neurotoxicity was simply additive. These results suggest a potential benefit in terms of overall efficacy versus toxicity for the combination of PHT and VPA, as compared with PHT or VPA used alone.
- Subjects :
- Phenytoin
Combination therapy
medicine.medical_treatment
Context (language use)
Pharmacology
Mice
Epilepsy
medicine
Animals
Drug Interactions
Pharmacology (medical)
Brain Diseases
Electroshock
Valproic Acid
business.industry
Neurotoxicity
Brain
Drug Synergism
Drug interaction
medicine.disease
Anticonvulsant
Female
lipids (amino acids, peptides, and proteins)
Neurology (clinical)
business
medicine.drug
Subjects
Details
- ISSN :
- 03625664
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- Clinical Neuropharmacology
- Accession number :
- edsair.doi.dedup.....38f714de6a3cdddd678d2b500dfc10af