title: Plasma concentration of flumazenil following intranasal administration in children.
abstract: OBJECTIVE
  A pharmacokinetic study in children to determine plasma flumazenil concentrations after the intranasal administration of 40 microg x kg(-1).
  
  
  METHODS
  Following institutional approval and informed written consent, 11 ASA physical status I-II patients, aged two to six years, undergoing general anesthesia for dental surgery were recruited. After induction, 40 microg x kg(-1) flumazenil Anexate, Roche, 0.1 mg x mL(-1) (0.4 mL x kg(-1))) were administered via a syringe as drops, prior to nasal intubation. Venous plasma samples were drawn prior to administration of flumazenil (t = 0), and then at 2, 4, 6, 8, 10, 15, 20, 30, 40, 60, and 120 min thereafter. The plasma samples were immediately processed by the on-site laboratory and then stored at -70 degrees C, before batch analysis via high performance liquid chromatography assay. Pharmacokinetic data calculations were performed using WinNonLin software (Scientific Consulting Inc.).
  
  
  RESULTS
  Eleven patients were studied, but data for one patient were discarded due to insufficient sampling. The median age was 4.3 yr (range 3 to 6), with a median weight of 18.9 kg (range 14.9 to 22.2). There were seven boys and three girls. Mean Cmax was 67.8 ng x mL(-1) (SD 41.9), with Tmax at two minutes. The calculated half-life was 122 min (SD 99).
  
  
  CONCLUSIONS
  The mean plasma concentrations of flumazenil attained were similar to those reported after intravenous administration, and may be sufficient to antagonize the side-effects of benzodiazepines. This route of administration may be useful when the intravenous route is not readily available.
authors.affiliation: Department of Anesthesia, University of British Columbia, Vancouver, Canada. louissch@home.iatronet.net
authors.forename: L D
authors.initials: LD
authors.lastname: Scheepers
authors.forename: C J
authors.initials: CJ
authors.lastname: Montgomery
authors.forename: A M
authors.initials: AM
authors.lastname: Kinahan
authors.forename: G S
authors.initials: GS
authors.lastname: Dunn
authors.forename: R A
authors.initials: RA
authors.lastname: Bourne
authors.forename: J P
authors.initials: JP
authors.lastname: McCormack
mesh_terms: D000281:Administration, Intranasal; D001569:Benzodiazepines / Q000037:antagonists & inhibitors*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005442:Flumazenil / Q000008:administration & dosage / Q000097:blood*; D018757:GABA Modulators / Q000097:blood*; D006801:Humans; D008297:Male
chemical_list: D018757:GABA Modulators; D001569:Benzodiazepines; D005442:Flumazenil