Antiepileptic drug combinations and experimental background: the case of phenobarbital and phenytoin

Naunyn-Schmiedeberg's Archives of Pharmacology
B F Bourgeois

Abstract

In view of the trend towards single drug therapy of epilepsy, the experimental background for thr combination of phenobarbital (PB) and phenytoin (PHT) was reassessed. Since potentiation of the anticonvulsant activity is in itself neither sufficient nor necessary to demonstrate the superiority of a drug combination, protection against maximal electroshock seizures as well as neurotoxicity were determined in mice. This allowed one to separate the neurotoxic from the anticonvulsant interaction and to base the analysis on changes in the therapeutic index (TI). Pharmacokinetic interactions were excluded from the analysis by expressing all results in terms of brain concentrations. The anticonvulsant interaction between PB and PHT was found to be additive, whereas the neurotoxic interaction was antagonistic. These results provide experimental documentation of one of the theories behind antiepileptic drug combinations. However, because PB had a markedly lower TI than PHT in this model, the TI of the drug combination was lower than the TI of PHT. Thus, the antagonism with regard to neurotoxicity was not sufficient to raise the TI of the combination above the TI of PHT.

References

Aug 1, 1978·Epilepsia·R L KrallE A Swinyard
Dec 1, 1975·The Journal of Antimicrobial Chemotherapy·D W KerryW Brumfitt
Jul 6, 1971·Annals of the New York Academy of Sciences·P L MorselliS Garattini
Jan 1, 1966·Archives of Neurology·P T WhiteJ Norton
Dec 1, 1983·Developmental Medicine and Child Neurology·H S BennettP Ziring
Aug 7, 1982·British Medical Journal·E Fischbacher
Dec 1, 1982·Journal of Neurology, Neurosurgery, and Psychiatry·D Schmidt
May 1, 1981·Drugs·E H Reynolds, S D Shorvon
Oct 18, 1952·Journal of the American Medical Association·M D YAHRH H MERRITT
Mar 1, 1957·Journal of the American Pharmaceutical Association·N W DUNHAM, T S MIYA

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Citations

Aug 6, 1991·European Journal of Pharmacology·E UrbańskaW A Turski
Jul 23, 2003·Pharmacology, Biochemistry, and Behavior·Jarogniew ŁuszczkiStanisław J Czuczwar
Nov 26, 2002·Epilepsy Research·Stanisław J Czuczwar, Kinga K Borowicz
Dec 10, 1998·British Journal of Pharmacology·O E Della PaschoaM Danhof
Jan 1, 1988·Epilepsia·B F Bourgeois
Oct 26, 1999·Epilepsia·C E Elger, G Fernández
Jul 26, 2010·Pharmaceuticals·Jong Woo Lee, Barbara Dworetzky
Feb 13, 2009·Expert Opinion on Drug Metabolism & Toxicology·Stanislaw J CzuczwarMarek Kacinski
Apr 25, 2000·Seizure : the Journal of the British Epilepsy Association·J P Leach
Jul 19, 2011·Epilepsy & Behavior : E&B·Martin J BrodieH Steve White
Jan 7, 2015·Critical Reviews in Analytical Chemistry·Monika WieczerzakJacek Namieśnik
Jul 20, 2018·Expert Review of Clinical Pharmacology·Barbara BłaszczykStanisław J Czuczwar
Jul 17, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jarogniew J LuszczkiStanisław J Czuczwar
Apr 30, 2017·The Journal of Trauma and Acute Care Surgery·Xi-Chun M LuFrank C Tortella
Jan 1, 2016·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·V A KarlovA V Lebedeva

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