title: Total Phenytoin concentration is not well correlated with active free drug in critically-ill head trauma patients.
abstract: OBJECTIVE
  Phenytoin is an antiepileptic drug used widely for prophylaxis and treatment of seizure after neurotrauma. Phenytoin has a complex pharmacokinetics and monitoring of its serum concentrations is recommended during treatment. Total phenytoin concentration is routinely measured for monitoring of therapy. In this study, we evaluated the correlation between phenytoin total and free concentrations in neurotrauma critically-ill patients to determine whether the phenytoin total concentration is a reliable predictor of free drug, which is responsible for the therapeutic effects.
  
  
  METHODS
  A total of 40 adult head trauma patients evaluated for free (unbound) and total serum phenytoin concentrations. Patients were divided into two groups. Group A consists of 20 unconscious patients with severe head injury under mechanical ventilation and Group B consists of 20 conscious self-ventilated patients. Correlation and agreement between total and free phenytoin plasma concentrations were analyzed.
  
  
  RESULTS
  Pearson correlation analysis and Bland-Altman test showed weak to moderate correlation (r = 0.528) and poor agreement between free and total phenytoin concentrations in patients with severe trauma and higher Acute Physiology And Chronic Health Evaluation II (APACHE II) scores (Group A) and good correlation (r = 0.817) and moderate agreement in patients with mild to moderate trauma and lower APACHE II scores (Group B).
  
  
  CONCLUSIONS
  Our results indicated that total phenytoin serum concentration is not a reliable therapeutic goal for drug monitoring in severely-ill head trauma patients even in the absence of hypoalbuminemia, renal and hepatic failure. It seems justifiable to measure free phenytoin concentration in all severely ill neurotrauma patients.
authors.affiliation: Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Kourosh
authors.initials: K
authors.lastname: Sadeghi
authors.affiliation: Department of Clinical Pharmacy, Islamic Azad University, Tehran, Iran.
authors.forename: Farin
authors.initials: F
authors.lastname: Hadi
authors.affiliation: Department of Anesthesia and Intensive Care, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Arezoo
authors.initials: A
authors.lastname: Ahmadi
authors.affiliation: Department of Clinical Pharmacy and Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Hamishehkar
authors.affiliation: Department of Anesthesia and Intensive Care, Imam-Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad-Taghi
authors.initials: MT
authors.lastname: Beigmohammadi
authors.affiliation: Department of Anesthesia and Intensive Care, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Ata
authors.initials: A
authors.lastname: Mahmoodpoor
authors.affiliation: Department of Biopharmaceutics and Pharmacokinetics, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Rouini
authors.affiliation: Students' Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Shirin
authors.initials: S
authors.lastname: Farhudi
authors.affiliation: Department of Clinical Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Narjes
authors.initials: N
authors.lastname: Hendoui
authors.affiliation: Department of Anesthesia and Intensive Care, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Atabak
authors.initials: A
authors.lastname: Najafi
authors.affiliation: Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran ; Department of Anesthesia and Intensive Care, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Mojtahedzadeh
keywords: Critically-ill patients; Phenytoin; free drug concentration; head trauma; hypoalbuminemia