title: Steady-state serum phenytoin concentrations after nasogastric tube administration of immediate-release phenytoin tablets and extended-release phenytoin capsules: an open-label, crossover, clinical trial.
abstract: BACKGROUND
  When phenytoin is prescribed for administration via nasogastric tube, immediate-release OR) phenytoin tablets are crushed before use and extended-release (ER) phenytoin capsules are opened and only the granules are used. However, it is unknown whether the same dose of these 2 different formulations will result in the same steady-state serum phenytoin concentration.
  
  
  OBJECTIVE
  The aim of this study was to determine whether ER phenytoin capsules can be used interchangeably with IR phenytoin tablets for prophylaxis of posttraumatic seizures.
  
  
  METHODS
  Inpatients at the neurosurgical ward at Prasat Neurological Institute, Bangkok, Thailand, between October 2004 and October 2005 were enrolled in the study. All patients were initially prescribed IR phenytoin tablets 300 mg/d as a maintenance dose for prophylaxis of posttraumatic seizures. The serum phenytoin concentration was measured after ≥5 days of treatment with IR phenytoin tablets 300 mg/d (two 50-mg tablets every 8 hours) that had been crushed before being administered concomitantly with a blenderized diet through the nasogastric tube. Without a washout period, the dosage form was changed to ER phenytoin capsules (three 100-mg capsules QD). The capsules were opened and the contents were administered concomitantly with the blenderized diet through the nasogastric tube for ≥5 days. The serum phenytoin concentration was again determined. The patients were closely monitored for seizures and adverse events (AEs).
  
  
  RESULTS
  Thirty-three patients enrolled in the study and 17 (10 women, 7 men; mean [SD] age, 62.94 [15.94] years [range, 18-89 years]) completed the study. The mean (SD) serum phenytoin concentrations after administration of phenytoin tablets and capsules were 6.03 (5.92) μg/mL and 3.80 (2.71) μg/mL, respectively (P = 0.019). The mean serum phenytoin concentrations, adjusted for low serum albumin concentrations after administration of tablets and capsules, were calculated and reported to be 10.33 (11.60) μg/mL and 6.28 (4.76) μg/mL, respectively (P = 0.035). The maximum phenytoin metabolic rate (Vmax) (assuming the substrate concentration at which the rate of metabolism is one half Vmax = 4 mg/L) after the administration of phenytoin tablets and capsules was 8.37 (2.42) mg/kg · d(-1) and 10.38 (6.48) mg/kg · d(-1), respectively. These values were not significantly different. All patients were seizure-free and no AEs were observed.
  
  
  CONCLUSIONS
  The steady-state serum phenytoin concentration was significantly lower with ER phenytoin capsules 300 mg/d than IR phenytoin tablets 300 mg/d administered via nasogastric feeding tube concomitantly administered with a blenderized diet in these neurosurgical patients. Key words: phenytoin nasogastric tube feeding extended-release capsule immediate-release tablet.
authors.affiliation: Department of Pharmacy (Clinical), Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Duangchit
authors.initials: D
authors.lastname: Panomvana
authors.affiliation: Department of Pharmacy (Clinical), Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Napanan
authors.initials: N
authors.lastname: Khummuenwai
authors.affiliation: Department of Pharmacy, Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Supasil
authors.initials: S
authors.lastname: Sra-Ium
authors.affiliation: Department of Medicine, Neurological Institute, Bangkok, Thailand.
authors.forename: Somchai
authors.initials: S
authors.lastname: Towanabut