title: Phenytoin dosing and serum concentrations in paediatric patients requiring 20 mg/kg intravenous loading.
abstract: BACKGROUND
  Phenytoin has complex pharmacokinetics. The intravenous loading dose of phenytoin for children in status epilepticus has recently been increased from 18 to 20 mg/kg. There are no data on the clinical effectiveness and safety of this new dose.
  
  
  METHODS
  The use of intravenous loading doses of phenytoin was audited over 27 months to evaluate the pharmacokinetic, clinical and toxic effects of the new dose in clinical practice. Serum phenytoin concentrations were compared with dose (weight-adjusted) and time.
  
  
  RESULTS
  Serum phenytoin concentrations were measured on 48 occasions from 41 children (39 retrospective and 9 prospective), of which 24 were within 60-180 (median 105) minutes following completion of infusion of the loading dose. Use of estimated weights meant patients received between 15.5 and 27.5 mg/kg (78% to 138% expected dose). Supra-therapeutic serum concentrations >20 µg/mL were present in 5/24 (20.1%) (after doses based on actual weight in three and estimated weight in two patients). Three adverse effects consistent with phenytoin toxicity were noted in children with supra-therapeutic concentrations. Two errors in dose prescriptions were found.
  
  
  CONCLUSIONS
  The majority of serum phenytoin concentrations were in the therapeutic range. Estimating weight in children for the 20 mg/kg intravenous loading dose of phenytoin is often clinically necessary but inaccurate, resulting in up to 138% of the expected and recommended dose in this cohort.
authors.affiliation: Department of Neurology, Alder Hey Children's Hospital, Liverpool, UK.
authors.forename: Joe D
authors.initials: JD
authors.lastname: Piper
authors.affiliation: Department of Women's and Children's Health, University of Liverpool, Liverpool, UK.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Hawcutt
authors.affiliation: Department of Neurology, Alder Hey Children's Hospital, Liverpool, UK.
authors.forename: George K
authors.initials: GK
authors.lastname: Verghese
authors.affiliation: Department of Neurology, Alder Hey Children's Hospital, Liverpool, UK.
authors.forename: Stefan
authors.initials: S
authors.lastname: Spinty
authors.affiliation: Department of Clinical Chemistry, Alder Hey Children's Hospital, Liverpool, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Newland
authors.affiliation: Department of Neurology, Alder Hey Children's Hospital, Liverpool, UK Department of Women's and Children's Health, University of Liverpool, Liverpool, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Appleton
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D054796:Drug Dosage Calculations; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010672:Phenytoin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011446:Prospective Studies; D012189:Retrospective Studies; D013226:Status Epilepticus / Q000188:drug therapy / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D010672:Phenytoin
keywords: Accident & Emergency; Audit; Neurology; Pharmacology; Therapeutics