title: Endotracheal flumazenil: a new route of administration for benzodiazepine antagonism.
abstract: The purpose of this study was to determine if flumazenil is absorbed from broncho-pulmonary tissue after intratracheal administration and whether therapeutically significant plasma concentrations can be obtained. Six elective surgical patients received a dose of 1.0 mg flumazenil in 10 mL saline intratracheally during general anesthesia. Blood samples were drawn for 6 hours after administration and plasma concentrations were determined by gas chromatography-mass spectrometry (GC-MS). An average peak plasma flumazenil concentration of 65.9 +/- 43.1 ng/mL was attained within 1 minute after administration. No patients reported chest discomfort or dyspnea upon awakening and there were no other side effects noted. Administration of flumazenil via an endotracheal tube results in rapid attainment of therapeutic blood levels.
authors.affiliation: Department of Medicinal Chemistry, University of Washington, Seattle 98195, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Palmer
authors.forename: D S
authors.initials: DS
authors.lastname: Mautz
authors.forename: K
authors.initials: K
authors.lastname: Cox
authors.forename: E D
authors.initials: ED
authors.lastname: Kharasch
mesh_terms: D000042:Absorption; D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000768:Anesthesia, General; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors; D000931:Antidotes / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics; D001569:Benzodiazepines / Q000037:antagonists & inhibitors*; D001980:Bronchi / Q000378:metabolism; D002637:Chest Pain / Q000517:prevention & control; D004417:Dyspnea / Q000517:prevention & control; D017558:Elective Surgical Procedures; D005260:Female; D005442:Flumazenil / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D005500:Follow-Up Studies; D018757:GABA Modulators / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007442:Intubation, Intratracheal; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014132:Trachea
chemical_list: D014151:Anti-Anxiety Agents; D000931:Antidotes; D018757:GABA Modulators; D001569:Benzodiazepines; D005442:Flumazenil