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Brain concentrations of phenytoin, phenobarbitone and primidone in epileptic patients

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Summary

Plasma, brain, lumbar CSF, skeletal muscle, skin and bone concentrations of phenytoin, phenobarbitone and primidone have been measured in specimens from patients undergoing temporal lobectomy for chronic epilepsy. A good correlation was found between the plasma and brain concentrations of each drug. Similarly, a good correlation was found between the plasma and CSF concentrations of each drug. Assuming that CSF is an ultrafiltrate of plasma, the percentage of phenytoin, phenobarbitone and primidone which was unbound in plasma was 10–14%, 43% and 81% respectively. Skeletal muscle concentrations of phenytoin and phenobarbitone and the skin concentration of phenytoin, also correlated with the plasma concentrations, but the remaining tissues did not give significant correlations.

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References

  • Andrew, R.L., Neubauer, L.G.: The distribution of barbiturates in the human body. Analyst.72, 21–22 (1947)

    Google Scholar 

  • Buchthal, F., Svensmark, O., Schiller, P.J.: Clinical and electroencephalographic correlation with serum levels of diphenylhydantoin. Arch. Neurol. (Chic.)2, 624–630 (1960)

    Google Scholar 

  • Falconer, M.A., Taylor, D.C.: Surgical treatment of drug-resistant epilepsy due to mesial temporal sclerosis. Arch. Neurol. (Chic.)19, 353–361 (1968)

    Google Scholar 

  • Gallagher, B.B., Baumel, I.P.: Primidone. Absorption, distribution, and excretion. In: Antiepileptic drugs (eds. D.M. Woodbury, J.K. Penry, R.P. Schmidt), pp. 357–359. New York: Raven Press 1972

    Google Scholar 

  • Johannessen, S., Strandjord, R.E.: Absorption and protein binding in serum of several anti-epileptic drugs. Proceedings of workshop on the determination of anti-epileptic drugs in body fluids II. Springer Verlag (in press) (1974)

  • Lund, L.: Anticonvulsant effect of diphenyl-hydantoin relative to plasma levels. A prospective 3 year study in ambulant patients with generalized epileptic seizures. Arch. Neurol. (Chic.)31 289–294 (1974)

    Google Scholar 

  • Lund, L., Berlin, A., Lunde, P.K.M.: Plasma protein binding of diphenylhydantoin in patients with epilepsy. Agreement between the unbound fraction in plasma and the concentration in cerebrospinal fluid. Clin. Pharmacol. Ther.13 196–200 (1972)

    Google Scholar 

  • Lunde, P.K.M., Rane, A., Yaffe, S.J., Lund, L., Sjöqvist, F.: Plasma protein binding of diphenylhydantoin in man. Interaction with other drugs and the effect of temperature and plasma dilution. Clin. Pharmacol. Ther.11 846–855 (1970)

    Google Scholar 

  • Mijamoto, K., Seino, M.: Simultaneous determination of twelve anti-epileptic drugs and their levels in blood and cerebrospinal fluid. Proceedings of workshop on the determination of anti-epileptic drugs in body fluids II. Springer Verlag (in press) (1974)

  • Odar-Cederlöf, I., Borgå, O.: Kinetics of diphenylhydantoin in uraemic patients: consequences of decreased plasma protein binding. Europ. J. clin. Pharmacol.7 31–37 (1974)

    Google Scholar 

  • Reynolds, E.H., Mattson, R.H., Gallagher, B.B.: Relationships between serum and cerebrospinal fluid anticonvulsant drug and folic acid concentrations in epileptic patients. Neurology (Minneap.)22 841–844 (1972)

    Google Scholar 

  • Sherwin, A.L., Eisen, A.A., Sokolowski, C.D.: Anticonvulsant drugs in human epileptogenic brain. Arch. Neurol. (Chic.)29 73–77 (1973)

    Google Scholar 

  • Thompson, A.: Urinary excretion of phenobarbitone after a single large dose. Lancet1950 I 70–71

    Google Scholar 

  • Toseland, P.A., Albani, M., Gauchel, F.D.: Nitrogen-selective gas-chromatographic determination of anticonvulsant drugs and barbiturates in plasma and tissues. Clin. Chem.21 98–103 (1975)

    Google Scholar 

  • Vajda, F., Williams, F.M., Davidson, S., Falconer, M.A., Breckenridge, A.: Human brain, cerebrospinal fluid, and plasma concentrations of diphenylhydantoin and phenobarbital. Clin. Pharmacol. Ther.15 597–603 (1974)

    Google Scholar 

  • Woodbury, D.M., Penry, J.K., Schmidt, R.P.: Antiepileptic drugs, New York: Raven Press 1972

    Google Scholar 

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Houghton, G.W., Richens, A., Toseland, P.A. et al. Brain concentrations of phenytoin, phenobarbitone and primidone in epileptic patients. Eur J Clin Pharmacol 9, 73–78 (1975). https://doi.org/10.1007/BF00613432

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  • DOI: https://doi.org/10.1007/BF00613432

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