Unbound Plasma Phenytoin Concentrations Measured Using Enzyme Immunoassay Technique on the Cobas MIRA Analyser—In Vivo Effect of Valproic Acid
作者:
Benedetta Sallustio,
Raymond Morris,
期刊:
Therapeutic Drug Monitoring
(OVID Available online 1992)
卷期:
Volume 14,
issue 1
页码: 9-13
ISSN:0163-4356
年代: 1992
出版商: OVID
关键词: Phenytoin protein binding;Therapeutic drug monitoring;Drug interaction
数据来源: OVID
摘要:
This communication describes a modification of the total plasma phenytoin enzyme immunoassay technique (EMIT) run on the Cobas MIRA analyser that allows quantitation of unbound phenytoin concentrations in human plasma for routine therapeutic drug monitoring (TDM) purposes. An application of this method is also presented to consider the previously described protein binding drug interaction with concomitantly administered valproic acid in patients with epilepsy. The coefficients of variation for the unbound phenytoin assay ranged from 7.5 to 9.6% and the assay had a reproducibility and accuracy similar to the total phenytoin assay, acceptable for routine TDM. Phenytoin protein binding was linear over a range of total plasma concentrations of 3–65 mg/L. Patients also receiving valproic acid (nine patients, 105 specimens) had a significantly (p< 0.0001) greater mean ± SD unbound phenytoin fraction (13.3 ± 3.1%) compared to nine patients (110 specimens) not receiving valproic acid (8.3 ± 1.6%). There was also a significant correlation (p< 0.001) between plasma valproic acid concentration and unbound phenytoin fraction, which resulted in greater intrasubject variability in phenytoin protein binding.
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