Advertisement

Pharmacy World and Science

, Volume 16, Issue 5, pp 217–224 | Cite as

Phenytoin pharmacokinetics after intravenous administration to patients receiving enteral tube feeding

  • Cameron T. C. Randall
  • Susan E. Tett
Articles

Abstract

Serial plasma samples were collected after administration of 13 intravenous doses of phenytoin to 11 patients with head injury; 5 to patients who had been receiving enteral feeds for less than 5 days (group 1), and 8 to patients who had been receiving enteral feeds for longer than 5 days (group 2). Average plasma phenytoin concentrations were higher in group 1 than in group 2 (p=0.003). The median intravenous study dose was the same (300 mg) in both groups (p=0.1 7). Group 2 received slightly higher doses expressed as mg/kg (median of 5.45 mg/kg compared to 4.29 mg/kg in group 1, p=0.21). Phenytoin was more rapidly eliminated following intravenous dosing in patients receiving long-term enteral feeding.Vmax was higher in group 2 than in group 1 (medians, 709versus 394 mg/day) andKm smaller (medians, 2.5versus 3.9 mg/l), but volume of distribution was similar in both groups (p=0.88). The kinetic parameters of phenytoin in group 1 were similar to previously published population pharmacokinetic parameters. In order to maintain phenytoin concentrations adequate for seizure prophylaxis in patients receiving longterm enteral feeding it would be advisable to decrease the dosing interval as well as increasing the phenytoin dose when the drug is administered intravenously.

Keywords

Clearance Enteral feeding Pharmacokinetics Phenytoin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    North JB, Hanieh A, Challen RG, Penhall RK, Hahn CS, Frewin DB. Postoperative epilepsy: a double-blind trial of phenytoin after craniotomy. Lancet 1980;1:384–6.Google Scholar
  2. 2.
    Temkin NR, Dikman SS, Wilensky AJ, Keihm J, Chabal S, Winn HR. A randomised, double-blind study of phenytoin for the prevention of post-traumatic seizures. N Engl J Med 1990;323:497–502.Google Scholar
  3. 3.
    Welty T, Horner TG. Pathophysiology and treatment of subarachnoid hemorrhage. Clin Pharm 1990;9:35–9.Google Scholar
  4. 4.
    Bauer LA. Interference of oral phenytoin absorption by continuous nasogastric feedings. Neurology 1982;32:570–2.Google Scholar
  5. 5.
    Cosh DG, Rowett DS, Lee PS, McCarthy PJ. Case report — phenytoin therapy complicated by concurrent chloramphenicol and enteral nutrition. Aust J Hosp Pharm 1987;17:51–3.Google Scholar
  6. 6.
    Guidry JR, Eastwood TF, Curry SC. Phenytoin absorption in volunteers receiving selected enteral feeding. West J Med 1989;150:659–61.Google Scholar
  7. 7.
    Hatton RC. Dietary interaction with phenytoin. Clin Pharm 1984;3:110–1.Google Scholar
  8. 8.
    Jann MW, Bean J, Fidone GS. Interaction of dietary pudding with phenytoin [letter]. Pediatrics 1986;78:952–3.Google Scholar
  9. 9.
    Longe R, Smith O. Phenytoin interaction with an oral feeding results in loss of seizure control. J Am Geriatr Soc 1988;36:542–4.Google Scholar
  10. 10.
    Maynard GA, Jones KM, Guidry JR. Phenytoin absorption from tube feedings. Arch Intern Med 1987;147:1821.Google Scholar
  11. 11.
    McGilvery J. Interaction of phenytoin and nasogastric feeds. Aust J Hosp Pharm 1985;15:128.Google Scholar
  12. 12.
    Ozuna J, Friel P. Effect of enteral tube feeding on serum phenytoin levels. J Neurosurg Nurs 1984;16:289–91.Google Scholar
  13. 13.
    Pearce GA. Apparent inhibition of phenytoin absorption by an enteral nutrition formula. Aust J Hosp Pharm 1988;18:289–92.Google Scholar
  14. 14.
    Saklad JJ, Graves RH, Sharp WP. Interaction of oral phenytoin with enteral feedings. J Parenter Enter Nutr 1986;10:322–3.Google Scholar
  15. 15.
    Weinryb J, Cogen R. Interaction of nasogastric phenytoin and enteral feeding solution. J Am Geriatr Soc 1989;37:195–6.Google Scholar
  16. 16.
    Worden JP, Wood CA, Workman CH. Phenytoin and nasogastric feeding [letter]. Neurology 1984;34:132.Google Scholar
  17. 17.
    Krueger KA, Garnett WR, Comstock TJ, Fitzsimmons WE, Karnes TH, Pellock JM. Effect of two administration schedules of an enteral nutrient formula on phenytoin bioavailability. Epilepsia 1987;28:706–12.Google Scholar
  18. 18.
    Marvel ME, Bertino JS. Comparative effects of elemental and complex feeding formulation on the absorption of phenytoin suspension. J Parent Enter Nutr 1991;15:316–8.Google Scholar
  19. 19.
    Nishimura LY, Armstrong EP, Plezia PM, Iaccono RP. Influence of enteral feeding on phenytoin sodium absorption from capsules. DICP 1988;22:130–3.Google Scholar
  20. 20.
    Cockcroft D, Gault M. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31–41.Google Scholar
  21. 21.
    Remmel RP, Miller SA, Graves NM. Simultaneous assays for felbamate plus carbamazepine, phenytoin and their metabolites by liquid chromatography with mobile phase optimisation. Ther Drug Monit 1990;12:90–6.Google Scholar
  22. 22.
    Godley PJ, Ludden TM, Clementi WA, Godley SE, Ramsey RR. Evaluation of a Bayesian regression-analysis computer program using non-steady-state phenytoin concentrations. Clin Pharm 1987;6:634–9.Google Scholar
  23. 23.
    Pulver LK, Tett SE, Montgomery WS. Clinical evaluation of a predictive model for phenytoin plasma concentrations. Aust J Hosp Pharm 1991;21:303–7.Google Scholar
  24. 24.
    Bauer LA, Blouin RA. Age and phenytoin kinetics in adult epileptics. Clin Pharmacol Ther 1982;31:301–4.Google Scholar
  25. 25.
    Grasela TH, Sheiner LB, Rambeck B, Boenigk HE, Dunlop A, Mullen PW, et al. Steady state pharmacokinetics of phenytoin from routinely collected patient data. Clin Pharmacokinet 1983;8:355–64.Google Scholar
  26. 26.
    Lund L. Anticonvulsant levels of diphenylhydantoin relative to plasma levels. Arch Neural 1974;31:289–94.Google Scholar
  27. 27.
    Vozeh S, Muir KT, Sheiner LB, Follath F. Predicting individual phenytoin dosage. J Pharmacokinet Biopharm 1981;9:131–46.Google Scholar
  28. 28.
    Messahel FM, Solis GL, Aguwa CN. Does parenteral nutrition lower serum phenytoin levels? Curr Ther Res 1990;47:1017–20.Google Scholar
  29. 29.
    Boucher BA, Rodman JH, Jaresko GS, Rasmussen SN, Watridge CB, Fabian TC. Phenytoin pharmacokinetics in critically ill trauma patients. Clin Pharmacol Ther 1988;44:675–83.Google Scholar
  30. 30.
    Hooper WD, Bochner F, Eadie MJ, Tyrer JH. Plasma protein binding of diphenylhydantoin, effect of sex hormones, renal and hepatic disease. Clin Pharmacol Ther 1974;15:276–82.Google Scholar
  31. 31.
    Winter ME, Tozer TN. Phenytoin. In: Evans WE, Schentag JJ, Jusko WJ, editors. Applied pharmacokinetics — principles of therapeutic drug monitoring. 2nd ed. Spokane: Applied Therapeutics, 1986:493–539.Google Scholar
  32. 32.
    Blum MR, Riegelman S, Becker CE. Altered protein binding of diphenylhydantoin in uraemic plasma. N Engl J Med 1972;286:109–11.Google Scholar
  33. 33.
    Peterson GM, Khoo BHC, Von Witt RJ. Clinical response in epilepsy in relation to total and free serum levels of phenytoin. Ther Drug Monitor 1991;13:415–9.Google Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1994

Authors and Affiliations

  • Cameron T. C. Randall
    • 1
  • Susan E. Tett
    • 2
  1. 1.Department of PharmacySt. Vincent's HospitalDarlinghurstAustralia
  2. 2.Department of Clinical Pharmacology & ToxicologySt. Vincent's HospitalDarlinghurstAustralia

Personalised recommendations