Plasma concentrations of flumazenil following intranasal administration inchildren

Purpose: A pharmacokinetic study in children to determine plasma flumazenil concentrations after the intranasal administration of 40 mu g.kg(-1). Methods: Following institutional approval and informed written consent, I I ASA physical status I-II patients, aged two to six years, undergoing gener al anesthesia for dental surgery were recruited. After induction, 40 mu g.k (-1) flumazenil Anexate(R), Roche, 0.1 mg.mL(-1) (0.4 mL.kg(-1))) were admi nistered via a syringe as drops, prior to nasal intubation. Venous plasma s amples 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 samp les were immediately processed by the onsite laboratory and then stored at -70 degrees C, before batch analysis via high performance liquid chromatogr aphy assay. Pharmacokinetic data calculations were performed using WinNonLi n software (Scientific Consulting Inc.). Results: Eleven patients were studied, but data for one patient were discar ded 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 C-max was 67.8 ng.mL(-1) (SD 41.9), with T-max at tw o minutes. The calculated half-life was 122 min (SD 99). Conclusion: The mean plasma concentrations of flumazenil attained were simi lar to those reported after intravenous administration, and may be sufficie nt to antagonize the side-effects of benzodiazepines. This route of adminis tration may be useful when the intravenous route is not readily available.