PHARMACODYNAMIC INTERACTIONS BETWEEN PHENYTOIN AND VALPROATE - INDIVIDUAL AND COMBINED ANTIEPILEPTIC AND NEUROTOXIC ACTIONS IN MICE

被引:26
作者
CHEZ, MG
BOURGEOIS, BFD
PIPPENGER, CE
KNOWLES, WD
机构
[1] CLEVELAND CLIN FDN,DEPT NEUROL,PEDIAT & ADOLESCENT NEUROL SECT,CLEVELAND,OH 44195
[2] CLEVELAND CLIN FDN,NEUROPHARMACOL & PEDIAT EPILEPSY,CLEVELAND,OH
[3] CLEVELAND CLIN FDN,DEPT BIOCHEM,CLEVELAND,OH 44195
[4] CLEVELAND CLIN FDN,DEPT NEUROSCI,CLEVELAND,OH
[5] CLEVELAND CLIN FDN,DEPT NEUROL,RES SECT,CLEVELAND,OH 44195
关键词
ANTIEPILEPTIC DRUGS; VALPROATE; PHENYTOIN; DRUG INTERACTIONS; MONOTHERAPY;
D O I
10.1097/00002826-199402000-00003
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:32 / 37
页数:6
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