Is free fraction measurement of phenytoin always necessary in pediatric epileptic patients?

Abstract:

:Sixty-two serum samples from 28 pediatric epileptic patients under treatment with phenytoin [diphenylhydantoin (DPH)] were obtained to study the correlation between total and free serum DPH concentrations. The effect of coadministered antiepileptic drugs on DPH protein binding was also studied. Binding of DPH to serum protein was assessed by ultrafiltration, and total and free DPH concentrations were determined by fluorescence polarization immunoassay. A strong correlation existed between the total and free concentrations [r = 0.958, p less than 0.001, standard error of estimate (+/- 1 SY) = 0.214]. The mean value for the DPH free fraction was 8.9% (range 5.7-16.3%). The samples obtained from patients on combination therapy with valproic acid (VPA) showed a larger DPH free fraction and greater variation. Exclusion of the 16 samples from patients concomitantly taking DPH and VPA yielded a better correlation (n = 46, r = 0.983, p less than 0.001, +/- 1 SY = 0.145). The mean free fraction in the patients not taking VPA was 7.7% (range 5.7-9.0%). The effect of VPA on the protein binding of DPH was also studied by addition of the same antiepileptic drugs to normal human plasma; the results were similar to those obtained for epileptic patients. These findings suggest that the free DPH fraction can be predicted from the total concentration, even when the drug is coadministered with other antiepileptic drugs, the sole exception being VPA.

journal_name

Ther Drug Monit

authors

Johno I,Kuzuya T,Suzuki K,Hasegawa M,Nakamura T,Kitazawa S,Aso K,Watanabe K

subject

Has Abstract

pub_date

1988-01-01 00:00:00

pages

39-44

issue

1

eissn

0163-4356

issn

1536-3694

journal_volume

10

pub_type

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