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. 1994 Jun;37(6):559–562. doi: 10.1111/j.1365-2125.1994.tb04304.x

Decreased plasma protein binding of valproate in patients with acute head trauma.

G D Anderson 1, B E Gidal 1, R J Hendryx 1, A B Awan 1, N R Temkin 1, A J Wilensky 1, H R Winn 1
PMCID: PMC1364815  PMID: 7917774

Abstract

1. One hundred and ten plasma samples were obtained from 50 patients treated with valproate for prophylaxis of post-traumatic head injuries. The samples were selected to include a wide range of albumin concentrations and were assayed for free and total valproate concentrations. Valproate binding parameters were determined from the Scatchard equation for one binding site using reweighted least squares analysis. 2. Plasma albumin concentrations were measured in 130 patients with head trauma. They started to decrease immediately after trauma, reaching a minimum at 5-7 days of approximately 24% of baseline value and did not return to normal until 1 month. 3. The free fraction of valproate varied six to seven-fold as albumin concentration ranged from 1.5 to 4.8 g 100 ml-1 (218-696 mumol l-1). The mean association constant for binding (Ka) was 0.008 mumol l(-1) and the mean number of binding sites (N) was 2.0. There values were similar to those reported for valproate in otherwise healthy patients with epilepsy. 4. Because of saturable protein binding of valproate, hypoalbuminaemia may necessitate the monitoring of free valproate concentrations to avoid toxicity when valproate is used in patients with acute head injury.

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Selected References

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  1. Battino D., Croci D., Granata T., Bernardi G., Monza G. Changes in unbound and total valproic acid concentrations after replacement of carbamazepine with oxcarbazepine. Ther Drug Monit. 1992 Oct;14(5):376–379. doi: 10.1097/00007691-199210000-00006. [DOI] [PubMed] [Google Scholar]
  2. Bauer L. A., Davis R., Wilensky A., Raisys V., Levy R. H. Valproic acid clearance: unbound fraction and diurnal variation in young and elderly adults. Clin Pharmacol Ther. 1985 Jun;37(6):697–700. doi: 10.1038/clpt.1985.116. [DOI] [PubMed] [Google Scholar]
  3. Bauer L. A., Edwards W. A., Dellinger E. P., Raisys V. A., Brennan C. Importance of unbound phenytoin serum levels in head trauma patients. J Trauma. 1983 Dec;23(12):1058–1060. doi: 10.1097/00005373-198312000-00007. [DOI] [PubMed] [Google Scholar]
  4. Boucher B. A., Rodman J. H., Jaresko G. S., Rasmussen S. N., Watridge C. B., Fabian T. C. Phenytoin pharmacokinetics in critically ill trauma patients. Clin Pharmacol Ther. 1988 Dec;44(6):675–683. doi: 10.1038/clpt.1988.211. [DOI] [PubMed] [Google Scholar]
  5. Bruni J., Wang L. H., Marbury T. C., Lee C. S., Wilder B. J. Protein binding of valproic acid in uremic patients. Neurology. 1980 May;30(5):557–559. doi: 10.1212/wnl.30.5.557-a. [DOI] [PubMed] [Google Scholar]
  6. Chadwick D. W. Concentration-effect relationships of valproic acid. Clin Pharmacokinet. 1985 Mar-Apr;10(2):155–163. doi: 10.2165/00003088-198510020-00003. [DOI] [PubMed] [Google Scholar]
  7. Cramer J. A., Mattson R. H., Bennett D. M., Swick C. T. Variable free and total valproic acid concentrations in sole- and multi-drug therapy. Ther Drug Monit. 1986;8(4):411–415. doi: 10.1097/00007691-198612000-00005. [DOI] [PubMed] [Google Scholar]
  8. Cramer J. A., Mattson R. H. Valproic acid: in vitro plasma protein binding and interaction with phenytoin. Ther Drug Monit. 1979;1(1):105–116. [PubMed] [Google Scholar]
  9. Gidal B. E., Collins D. M., Beinlich B. R. Apparent valproic acid neurotoxicity in a hypoalbuminemic patient. Ann Pharmacother. 1993 Jan;27(1):32–35. doi: 10.1177/106002809302700107. [DOI] [PubMed] [Google Scholar]
  10. Griebel M. L., Kearns G. L., Fiser D. H., Woody R. C., Turley C. P. Phenytoin protein binding in pediatric patients with acute traumatic injury. Crit Care Med. 1990 Apr;18(4):385–391. doi: 10.1097/00003246-199004000-00007. [DOI] [PubMed] [Google Scholar]
  11. Gugler R., Mueller G. Plasma protein binding of valproic acid in healthy subjects and in patients with renal disease. Br J Clin Pharmacol. 1978 May;5(5):441–446. doi: 10.1111/j.1365-2125.1978.tb01652.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Johno I., Huang M. Y., Levy R. H. Systemic interaction between valproic acid and free fatty acids in rhesus monkeys. Epilepsia. 1982 Dec;23(6):649–656. doi: 10.1111/j.1528-1157.1982.tb05080.x. [DOI] [PubMed] [Google Scholar]
  13. Kodama Y., Koike Y., Kimoto H., Yasunaga F., Takeyama M., Teraoka I., Fujii I. Binding parameters of valproic acid to serum protein in healthy adults at steady state. Ther Drug Monit. 1992 Feb;14(1):55–60. doi: 10.1097/00007691-199202000-00009. [DOI] [PubMed] [Google Scholar]
  14. Kodama Y., Kuranari M., Tsutsumi K., Kimoto H., Fujii I., Takeyama M. Prediction of unbound serum valproic acid concentration by using in vivo binding parameters. Ther Drug Monit. 1992 Oct;14(5):349–353. doi: 10.1097/00007691-199210000-00001. [DOI] [PubMed] [Google Scholar]
  15. Koerner M., Yerby M., Friel P., McCormick K. Valproic acid disposition and protein binding in pregnancy. Ther Drug Monit. 1989;11(3):228–230. doi: 10.1097/00007691-198905000-00002. [DOI] [PubMed] [Google Scholar]
  16. Kushner I. The phenomenon of the acute phase response. Ann N Y Acad Sci. 1982;389:39–48. doi: 10.1111/j.1749-6632.1982.tb22124.x. [DOI] [PubMed] [Google Scholar]
  17. Levy R. H. Monitoring of free valproic acid levels? Ther Drug Monit. 1980;2(2):199–201. doi: 10.1097/00007691-198004000-00015. [DOI] [PubMed] [Google Scholar]
  18. McClain C. J., Hennig B., Ott L. G., Goldblum S., Young A. B. Mechanisms and implications of hypoalbuminemia in head-injured patients. J Neurosurg. 1988 Sep;69(3):386–392. doi: 10.3171/jns.1988.69.3.0386. [DOI] [PubMed] [Google Scholar]
  19. Perucca E. Free level monitoring of antiepileptic drugs. Clinical usefulness and case studies. Clin Pharmacokinet. 1984 Jan;9 (Suppl 1):71–78. doi: 10.2165/00003088-198400091-00009. [DOI] [PubMed] [Google Scholar]
  20. Perucca E., Grimaldi R., Gatti G., Pirracchio S., Crema F., Frigo G. M. Pharmacokinetics of valproic acid in the elderly. Br J Clin Pharmacol. 1984 Jun;17(6):665–669. doi: 10.1111/j.1365-2125.1984.tb02401.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Riva R., Albani F., Cortelli P., Gobbi G., Perucca E., Baruzzi A. Diurnal fluctuations in free and total plasma concentrations of valproic acid at steady state in epileptic patients. Ther Drug Monit. 1983 Jun;5(2):191–196. doi: 10.1097/00007691-198306000-00007. [DOI] [PubMed] [Google Scholar]
  22. Sadahiro N., Kodama S., Matsui T., Komatsu M., Matsuo T. Effect of serum albumin on free fractions of phenobarbital and valproic acid in patients with convulsive seizures. Brain Dev. 1985;7(4):377–384. doi: 10.1016/s0387-7604(85)80134-0. [DOI] [PubMed] [Google Scholar]
  23. Scheyer R. D., Cramer J. A., Toftness B. R., Hochholzer J. M., Mattson R. H. In vivo determination of valproate binding constants during sole and multi-drug therapy. Ther Drug Monit. 1990 Mar;12(2):117–123. [PubMed] [Google Scholar]
  24. Semmes R. L., Shen D. D. Capillary gas chromatographic assay for valproic acid and its 2-desaturated metabolite in brain and plasma. J Chromatogr. 1988 Nov 18;432:185–197. doi: 10.1016/s0378-4347(00)80644-1. [DOI] [PubMed] [Google Scholar]
  25. Yu H. Y. Clinical implications of serum protein binding in epileptic children during sodium valproate maintenance therapy. Ther Drug Monit. 1984;6(4):414–423. doi: 10.1097/00007691-198412000-00006. [DOI] [PubMed] [Google Scholar]

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