Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-26T10:15:16.764Z Has data issue: false hasContentIssue false

Distribution of Anticonvulsant Drugs in Gray and White Matter of Human Brain

Published online by Cambridge University Press:  15 November 2018

C. D. Harvey
Affiliation:
Department of Neurology and Neuro-surgery, McGill Universityand the Montreal Neurological Institute, and the Department of Clinical Pharmacy, University of Nijmegan
A. L. Sherwin*
Affiliation:
Department of Neurology and Neuro-surgery, McGill Universityand the Montreal Neurological Institute, and the Department of Clinical Pharmacy, University of Nijmegan
E. van der Kleun
Affiliation:
Department of Neurology and Neuro-surgery, McGill Universityand the Montreal Neurological Institute, and the Department of Clinical Pharmacy, University of Nijmegan
*
Neuro-pharmacology Laboratory, Montreal Neurological Institute, 3801 University Street, Montreal, Quebec H3A 2B4, Canada
Rights & Permissions [Opens in a new window]

Summary

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Gray and white matter were obtained during neurosurgical therapy of focal epilepsy from 17 patients. In 10 patients, receiving only phenobarbital, the drug was uniformly distributed between gray and white matter. Phenytoin concentrations averaged 1.4-fold greater in white matter than in gray matter when expressed per gram wet weight of tissue. The gray matter/plasma ratio of phenytoin was approximately 2-fold greater than that of phenobarbital. Carbamazepine levels were also slightly greater in white matter The data revealed wide differences between drugs in the relative concentrations in gray and white matter, which must be taken into account in any quantitative studies of anticonvulsant drug levels in the brain.

Résumé

Résumé

Nous avons étudié des échantillons de cortex cérébral et de substance blanche obtenus de 17 malades opérés pour une épilepsie focale. Dix d’entre eux ne recevaient que du phénobarbital et la concentration de cette drogue était égale au niveau du cortex et de la substance blanche. Exprimée par gamme de tissue frais, la concentration de phénytoine s’est avérée en moyenne 1.4 fois plus élevée au niveau de la substance blanche que de la matière grise Le rapport matière grise/plasma est environ 2 fois plus grand pour la phénytoine que pour le phénobarbital. La concentration de Carbamazepine est aussi légèrement plus élevée au niveau de la substance blanche. Ces données démontrent des différences marquées entre ces drogues substance blanche. Differences dont on doit tenir compte dans l’interprétation des études neurophysiologiques ou neuropharma-cologiques de la concentration cérébrale des drogues antiépileptiques.

Type
Research Article
Copyright
Copyright © Canadian Neurological Sciences Federation 1977

References

Baumel, I. P., Gallagher, B. B., Dimicco, J. and Goico, H. (1973) Metabolism and anticonvulsant properties of primidone in the rat. J. Pharmacol. Exp. Ther., 186, 305314.Google Scholar
Bush, M. T. and Sanders-Bush, E. (1972). Phenobarbital, mephobarbital, and metharbital, and their metabolites: chemistry and methods for determination. In: Woodbury, D. M., Penry, J. K. and Schmidt, R. P., editors: Antiepileptic drugs. New York, Raven Press, 293302.Google Scholar
Eichelbaum, M., Bertilsson, L., Lund, L., Palmer, L. and Sjoqvist, F. (1976). Plasma levels of carbamazepine and carbamazepine-10. 11-epoxide during treatment of epilepsy Europe. J. Clin. Pharmacol., 9. 417421.Google Scholar
Goldberg, M. A. and Todoroff, T. (1976). Enhancement of diphenylhydantoin binding by lipid extraction. J. Pharmacol. Exp. Ther., 196, 579585.Google ScholarPubMed
Houghton, G.W., Richens, A., Toseland, P. A., Davidson, S. and Falconer, M. A. (1975). Brain concentrations of phenytoin, phenobarbitone and primidone in epileptic patients. Europ. J. Clin. Pharmacol., 9. 7378.Google Scholar
Kupferberg, H. J. (1970). Quantitative estimation of diphenylhydantoin, primidone and phenobarbital in plasma by gas-liquid chromatography Clin. Chim. Acta. 29. 283288.CrossRefGoogle ScholarPubMed
Kupferberg, H J and Yonekawa, W. (1975). The metabolism of 3-methyl-5-ethyl-5-phenylhydantoin (mephenytoin) to 5-ethyl-5-phenylhydantoin (nirvanol) in mice in relation to anticonvulsant activity Drug Metab. Dispos., 3, 2629.Google Scholar
Leppik, I. E. and Sherwin, A. L. (In Press). Anticonvulsant activity of phenobarbital and phenytoin in combination. J. Pharmacol. Exp. Therap.Google Scholar
Maynert, E. W. (1972). Phenobarbital, mephobarbital, and metharbital: Absorption, distribution, and excretion. In: Woodbury, D. M., Penry, J. K., and Schmidt, R. P., editors: Antiepileptic Drugs, New York. Raven Press, 303310.Google Scholar
Morselli, P. L. (1975). Carbamazepine: absorption, distribution and excretion. In: Penry, J. K. and Daly, D. D., editors: Advances in Neurology, Vol. II: Complex partial seizures and their treatment. New York. Raven Press, 279292.Google Scholar
Rapport, R. L., Harris, A. B., Friel, P N and Ojemann, G. A. (1975). Human epileptic brain: Na, K. ATPase activity and phenytoin concentrations, Arch Neurol., 32, 549554.Google Scholar
Roth, L. J. and Barlow, C. F. (1961) Drugs in the brain, Science, 134, 2231.CrossRefGoogle ScholarPubMed
Sherwin, A. L., Eisen, A. A. and sokolowski, C. D. (1973). Anticonvulsant drugs in human epileptogenic brain Correlation of phenobarbital and diphenylhydantoin levels with plasma Arch. Neurol., 29, 7379.Google Scholar
Vajda, F. Williams, F. M., Davidson, S., Falconer, M. A. and Breckenridge, A. (1974). Human brain, cerebrospinal fluid, and palsma concentrations of diphenylhydantoin and phenobarbital. Clin. Pharmacol. Ther. 15, 597603.Google Scholar
Westenberg, H. G. and De Zeeuw, R. A. (1976). Rapid and sensitive liquid Chromatographic determination of carbamazepine suitable for use in monitoring multiple-drug anticonvulsant therapy, J. Chromatogr., 118, 217224.CrossRefGoogle ScholarPubMed