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Phenytoin Michaelis-Menten Pharmacokinetics in Caucasian Paediatric Patients

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Summary

The Michaelis-Menten pharmacokinetic parameters Vmax and Km were calculated for 135 epileptic paediatric patients receiving phenytoin as their only anticonvulsant therapy. Mean Vmax and Km values were 13.95 mg/kg/day and 6.59 μg/ml for 0.5 to 3-year-old patients, 10.93 mg/kg/day and 6.82 μg/ml for the 4 to 6 year age group, 10.05 mg/kg/day and 6.51 μg/ml for the 7 to 9-year-olds, and 8.25 mg/kg/day and 5.69 μg/ml for the 10 to 16 year group. Using analysis of variance, the Vmax values were significantly different (p < 0.01) but the Km values were not. Linear regression analysis of Vmax versus age revealed a significant decline in Vmax with age (r = −0.554; p < 0.001). A plot of Km versus age showed a poor correlation (r = −0.170) and a large amount of variability.

Based on this data, the youngest age group would require on average 62% more phenytoin/kg/day than the oldest age group in order to maintain a steady-state phenytoin concentration of 15 μg/ml. Because of these age-related pharmacokinetic differences, phenytoin dosages may require adjustment as paediatric patients become older.

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References

  • Andoh, B.; Idle, J.R.: Sloan, T.P.: Smith, R.L. and Woolhouse, N.: Interethnic and interphenotype difference among Ghanaians and Caucasians in the metabolic hydroxylation of phenytoin. British Journal of Clinical Pharmacology 9: 282P–283P (1980).

    Article  Google Scholar 

  • Blain, P.G.; Mucklow, J.C.; Bacon, C.J. and Rawlins, M.D.: Pharmacokinetics of phenytoin in children. British Journal of Clinical Pharmacology 12: 659–661 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Borofsky, L.G.; Louis, S.; Kurt, H. and Roginsky, M.: Diphenylhydantoin efficacy, toxicity, and dose-serum level relationships in children. Journal of Pediatrics 81: 995–999 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Buchthal, F.; Svensmark, O. and Schiller, P.J.: Clinical and electroencephalographic correlations with serum levels of diphcnylhydantoin. Archives of Neurology 2: 624–631 (1960).

    Article  PubMed  CAS  Google Scholar 

  • Chiba, K.; Ishizaki, T.; Miura, H. and Minagawa, K.: Michaelis-Menten pharmacokinetics of diphenylhydantoin and application in the pediatric age patient. Journal of Pediatrics 96: 479–484 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Dodson, W.E.: Nonlinear kinetics of phenytoin in children. Neurology 32: 42–48 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Eadic, M.J.: Tyrer, J.H.; Bochner, F. and Hooper, W.D.: The elimination of phenytoin in man. Clinical and Experimental Pharmacology and Physiology 3: 217–224 (1976).

    Article  Google Scholar 

  • Grasela, T.H.; Sheiner, L.B.; Rambeck, B.; Boenigk, H.E.; Dunlop, A.; Mullen, P.W.; Wadsworth, J.; Richens, A.; Ishizaki, T.: Chiba, K.; Miura, H.; Minagawa, K.; Blain, P.G.; Mucklow, J.C.; Bacon, C.T. and Rawlins, M.: Steady-state pharmacokinetics of phenytoin from routinely collected patient data. Clinical Pharmacokinetics 8: 355–364 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Kromann, N.; Christiansen, J.; Flacks, H.; Dam, M. and Hvidberg, E.F.: Differences in single dose phenytoin kinetics between Greenland Eskimos and Danes. Therapeutic Drug Monitoring 3: 239–245 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Lee, H.S. and Chan, K.Y.: Phenytoin and phenobarbitone plasma level-dose relationships in Chinese epileptic children in Singapore. Therapeutic Drug Monitoring 3: 247–252 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Ludden, T.M.; Allen, J.P.; Valutsky, W.A.; Vicuna, A.V.; Nappi, J.M.; Hoffman, S.F.; Wallace, J.E.; Lalka, D. and McNay, J.L.: Individualization of phenytoin dosage regimens. Clinical Pharmacology and Therapeutics 21: 287–291 (1977).

    PubMed  CAS  Google Scholar 

  • MacGee, J.: Rapid determination of diphenylhydantoin in blood plasma by gas Chromatograph. Analytical Chemistry 42: 421–422 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Martin, E.; Tozer, T.N.: Sheiner, L.B. and Riegelman, S.: The clinical pharmacokinetics of phenytoin. Journal of Pharmacokinetics and Biopharmaceutics 5: 579–591 (1977).

    PubMed  CAS  Google Scholar 

  • Rambcck, B.: Boenigk, H.E.; Dunlop, A.; Mullen, P.W.; Wadsworth, J. and Richens, A.: Predicting phenytoin dose — a revised nomogram. Therapeutic Drug Monitoring 1: 325–333 (1979).

    Article  Google Scholar 

  • Sheiner, L.B. and Beal, S.L.: Evaluation of methods for estimating population pharmacokinetic parameters. I. Michaelis-Menten model: Routine clinical data. Journal of Pharmacokinetics and Biopharmaceutics 8: 553–571 (1980).

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. School of Pharmacy, University of Washington, Seattle, and College of Pharmacy, University of Kentucky, Lexington, USA

    Larry A. Bauer & Robert A. Blouin

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  1. Larry A. Bauer
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  2. Robert A. Blouin
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Bauer, L.A., Blouin, R.A. Phenytoin Michaelis-Menten Pharmacokinetics in Caucasian Paediatric Patients. Clin Pharmacokinet 8, 545–549 (1983). https://doi.org/10.2165/00003088-198308060-00006

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