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Therapeutic Drug Monitoring of Phenytoin in Critically Ill Patients
Author(s) -
Winckelmann Sandrina L.,
Spriet Isabel,
Willems Ludo
Publication year - 2008
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.28.11.1391
Subject(s) - phenytoin , hypoalbuminemia , therapeutic drug monitoring , medicine , drug , pharmacokinetics , pharmacology , therapeutic index , critically ill , drug interaction , intensive care medicine , epilepsy , psychiatry
Therapeutic drug monitoring of phenytoin is necessary to ensure therapeutic and nontoxic levels. Hypoalbuminemia, renal failure, and interactions with other highly protein‐bound drugs (e.g., valproic acid) alter protein binding of phenytoin. When these conditions are present, free serum concentrations, which represent the pharmacologically active entity, cannot be predicted from total serum concentrations. Besides general alterations in drug distribution and elimination, protein binding is often altered in critically ill patients. Case reports describe phenytoin toxicity secondary to inappropriate dosage adjustments based solely on total serum concentrations in patients with hypoalbuminemia. Free drug measurements and theoretical equations to facilitate the interpretation of total phenytoin serum levels have been introduced. However, they are not widely implemented in clinical practice because evidence of improvements in patient outcomes is limited. Knowledge of the pharmacokinetic properties of phenytoin is indispensable for correct interpretation of total serum concentrations when protein binding is altered. Free serum concentrations should be measured, or theoretically calculated if measurements are unavailable, to avoid misinterpretation of total serum levels and consequent inappropriate adjustments in the dosage of phenytoin in critically ill patients.