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Displacement of phenytoin from plasma binding sites by salicylate
Author(s) -
Fraser D G,
Ludden T M,
Evens R P,
Sutherland Earl W
Publication year - 1980
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1980.25
Subject(s) - phenytoin , aspirin , sodium salicylate , crossover study , free fraction , chemistry , blood sampling , pharmacology , pharmacokinetics , medicine , anesthesia , epilepsy , alternative medicine , pathology , psychiatry , placebo
Six healthy male subjects received phenytoin sodium as 9 100‐mg capsules alone or with aspirin in a randomized, crossover fashion. Aspirin, 975 mg every 6 hr, was started 22 hr before a phenytoin dose and continued for an additional 48 hr during blood sampling. Mean 4‐hr plasma salicylate levels ranged from 104 to 157 μg/ml during the sampling period. Individual mean values for the free fraction of salicylate varied from 0.107 to 0.167. The fraction of free phenytoin in plasma rose from 0.128 ± 0.004 to 0.163 ±0.009 when aspirin was given (p < 0.001). Subjects had lower total phenytoin 48‐hr area under the curve (AUC) values when on aspirin (323 ± 36 without and 261 ± 49 μg · hr · ml −1 with aspirin; p < 0.001) but free phenytoin AUC values were unchanged (41.4 ± 4.5 and 42.4 ±9.0 μg · hr · ml −1 ; p > 0.5). Thus, more rapid clearance of total phenytoin probably compensated for salicylate displacement of phenytoin from plasma protein binding sites. Total phenytoin levels for therapeutic monitoring must be interpreted cautiously when patients also receive salicylate. Clinical Pharmacology and Therapeutics (1980) 27 , 165–169; doi: 10.1038/clpt.1980.25