Abstract
The plasma protein binding of phenytoin was studied in nine epileptic patients before and during addition of sodium valproate to the drug therapy. The free phenytoin fraction in plasma was significantly greater during sodium valproate treatment. The mean free fraction rose from 0.135 +/- 0.019 (s.d.) to 0.182 +/- 0.030. Total plasma phenytoin concentration fell significantly from a range of 4.3-26.2 micrograms/ml to 3.4-19.8 micrograms/ml during sodium valproate treatment. Neither the free plasma concentration nor the saliva concentration of phenytoin was significantly altered by sodium valproate. No significant correlation was found between plasma valproic acid concentrations and the change in phenytoin binding. We conclude that valproic acid displaces phenytoin from plasma protein binding sites but does not inhibit its metabolism.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bruni J., Gallo J. M., Lee C. S., Perchalski R. J., Wilder B. J. Interactions of valproic acid with phenytoin. Neurology. 1980 Nov;30(11):1233–1236. doi: 10.1212/wnl.30.11.1233. [DOI] [PubMed] [Google Scholar]
- Dahlqvist R., Borgå O., Rane A., Walsh Z., Sjöqvist F. Decreased plasma protein binding of phenytoin in patients on valproic acid. Br J Clin Pharmacol. 1979 Dec;8(6):547–552. doi: 10.1111/j.1365-2125.1979.tb01042.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Doumas B. T., Watson W. A., Biggs H. G. Albumin standards and the measurement of serum albumin with bromcresol green. Clin Chim Acta. 1971 Jan;31(1):87–96. doi: 10.1016/0009-8981(71)90365-2. [DOI] [PubMed] [Google Scholar]
- Knott C., Hamshaw-Thomas A., Reynolds F. Phenytoin-valproate interaction: importance of saliva monitoring in epilepsy. Br Med J (Clin Res Ed) 1982 Jan 2;284(6308):13–16. doi: 10.1136/bmj.284.6308.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kupferberg H. J. Quantitative estimation of diphenylhydantoin, primidone and phenobarbital in plasma by gas-liquid chromatography. Clin Chim Acta. 1970 Aug;29(2):282–288. doi: 10.1016/0009-8981(70)90048-3. [DOI] [PubMed] [Google Scholar]
- Mattson R. H., Cramer J. A., Williamson P. D., Novelly R. A. Valproic acid in epilepsy: clinical and pharmacological effects. Ann Neurol. 1978 Jan;3(1):20–25. doi: 10.1002/ana.410030105. [DOI] [PubMed] [Google Scholar]
- Monks A., Boobis S., Wadsworth J., Richens A. Plasma protein binding interaction between phenytoin and valproic acid in vitro. Br J Clin Pharmacol. 1978 Dec;6(6):487–492. doi: 10.1111/j.1365-2125.1978.tb00871.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Monks A., Richens A. Effect of single doses of sodium valproate on serum phenytoin levels and protein binding in epileptic patients. Clin Pharmacol Ther. 1980 Jan;27(1):89–95. doi: 10.1038/clpt.1980.14. [DOI] [PubMed] [Google Scholar]
- Perucca E., Hebdige S., Frigo G. M., Gatti G., Lecchini S., Crema A. Interaction between phenytoin and valproic acid: plasma protein binding and metabolic effects. Clin Pharmacol Ther. 1980 Dec;28(6):779–789. doi: 10.1038/clpt.1980.235. [DOI] [PubMed] [Google Scholar]
- Pisani F., Di Perri R., Nistico G. Rapid quantitation of N-dipropylacetamide in human plasma by gas-liquid chromatography. J Chromatogr. 1979 Jun 1;174(1):231–233. doi: 10.1016/s0021-9673(00)87059-4. [DOI] [PubMed] [Google Scholar]
- Sackellares J. C., Lee S. I., Dreifuss F. E. Stupor following administration of valproic acid to patients receiving other antiepileptic drugs. Epilepsia. 1979 Dec;20(6):697–703. doi: 10.1111/j.1528-1157.1979.tb04853.x. [DOI] [PubMed] [Google Scholar]