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Predicting individual phenytoin dosage

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Abstract

Most previously suggested methods for predicting phenytoin dosage from steady-state drug levels (Cpss)measured in the clinical setting fail to fully exploit all relevant (population) information. A Bayesian prediction method, applicable to any drug, is available. It appropriately combines all types of information. In this paper, we compare the Bayesian method as applied to phenytoin to two other prediction methods (and a baseline, nonfeedback one). Actual doses are compared to predictions in 49 patients. Each method is optimized, as far as possible, for the test data. The comparison favors the Bayesian method. Since each of the other prediction methods for phenytoin can be shown to be a theoretically suboptimal special case of the Bayesian one, the superiority of the latter may be a general phenomenon. Because the pharmacokinetic model linking steady-state phenytoin levels and dosage is so simple, a good approximation of the general Bayesian method can be implemented as a graphical device, or as a program for a programmable calculator. We present and describe both of these approximations.

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References

  1. A. J. Glazko, T. Chang, J. Bouhema, W. A. Dill, J. R. Goulet, and R. A. Buchanan. Metabolic disposition of diphenylhydantoin in normal human subjects following intravenous administration.Clin. Pharmacol. Ther. 10:498–504 (1969).

    CAS  PubMed  Google Scholar 

  2. H. Kutt and F. McDowell. Management of epilepsy with diphenylhydantoin.JAMA 203:969–972 (1968).

    Article  CAS  PubMed  Google Scholar 

  3. H. Kutt and F. McDowell. Pharmacodynamic and pharmacokinetic measurements of antiepileptic drugs.Clin. Pharmacol. Ther. 16:243–250 (1974).

    CAS  PubMed  Google Scholar 

  4. L. Lund. Anticonvulsant effect of diphenylhydantoin relative to plasma levels.Arch. Neurol. 31:289–294 (1974).

    Article  CAS  PubMed  Google Scholar 

  5. T. M. Ludden, J. P. Allen, W. A. Valutzky, A. V. Vicuna, J. M. Nappi, S. F. Hoffman, J. E. Wallace, D. Lalka, and J. L. McNay. Individualization of phenytoin dosage regimens.Clin. Pharmacol. Ther. 21:287–293 (1977).

    CAS  PubMed  Google Scholar 

  6. E. Martin, T. N. Tozer, L. B. Sheiner, and S. Riegelman. The clinical pharmacokinetics of phenytoin.J. Pharmacokin. Biopharm. 5:579–595 (1977).

    Article  CAS  Google Scholar 

  7. P. W. Mullen. Optimal phenytoin therapy: a new technique for individualizing dosage.Clin. Pharmacol. Ther. 23:228–232 (1978).

    CAS  PubMed  Google Scholar 

  8. A. Richens and A. Dunlop. Serum-phenytoin levels in management of epilepsy.Lancet II:247–248 (1975).

    Article  Google Scholar 

  9. B. Rambeck, H. E. Boenigk, A. Dunlop, P. W. Mullen, J. Wadsworth, and A. Richens. Predicting phenytoin dose—a revised nomogram.Ther. Drug Monit. 1:325–333 (1979).

    Article  CAS  PubMed  Google Scholar 

  10. L. B. Sheiner, S. Beal, B. Rosenberg, and V. Marathe. Forecasting individual pharmacokinetics.Clin. Pharmacol. Ther. 26:294–305 (1979).

    CAS  PubMed  Google Scholar 

  11. L. B. Sheiner, B. Rosenberg, and K. L. Melmon. Modelling individual pharmacokinetics for computer-aided drug dosage.Comp. Biomed. Res. 5:441–459 (1972).

    Article  Google Scholar 

  12. S. Vozeh, A. Koelz, E. Martin, H. Magun, G. Scollo-Lavizzari, and F. Follath. Predictability of phenytoin serum levels by nomograms and clinicians.Eur. Neurol. (1980), in press.

  13. J. Gordos, J. Schaublin, and P. Spring. Micro-determination of plasma diphenylhydantoin by gas-liquid chromatography.J. Chromatogr. 143:171–181 (1977).

    Article  CAS  PubMed  Google Scholar 

  14. A. Richens. A study of the pharmacokinetics of phenytoin (diphenylhydantoin) in epileptic patients, and the development of a nomogram for making dose increments.Epilepsia 16:627–646 (1975).

    Article  CAS  PubMed  Google Scholar 

  15. L. Lund and G. Alvan. Phenytoin dosage nomogram (letter).Lancet II:1305 (1975).

    Article  Google Scholar 

  16. S. Beal and L. B. Sheiner.NONMEM Users Guide — Part I. Technical Report, Div. Clinical Pharmacology, University of California, San Francisco, California (1979).

    Google Scholar 

  17. D. S. Salsburg. Estimating differences in variance when comparing two methods of assay.Technometrics 17:381–382 (1975).

    Article  Google Scholar 

  18. M. M. Reidenberg, I. Odar-Cederloff, C. Von Bahr, O. Borga, and F. Sjoqvist. Protein binding of diphenylhydantoin and desmethylimpramine in plasma from patients with poor renal function.N. Engl. J. Med. 285:264–267 (1971).

    Article  CAS  PubMed  Google Scholar 

  19. J. G. Wagner. Time to reach steady-state and prediction of steady-state concentrations for drugs obeying Michaelis-Menten elimination kinetics.J. Pharmacokin. Biopharm. 5:209–225 (1978).

    Article  Google Scholar 

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Work supported in part by USDHEW Grants GM 00001, GM 16496, and GM 26676, and by the Swiss National Research Foundation.

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Vozeh, S., Muir, K.T., Sheiner, L.B. et al. Predicting individual phenytoin dosage. Journal of Pharmacokinetics and Biopharmaceutics 9, 131–146 (1981). https://doi.org/10.1007/BF01068078

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  • DOI: https://doi.org/10.1007/BF01068078

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