title: The early kinetics of gentamicin uptake into the inner ear.
abstract: Transtympanic gentamicin administration has become a popular modality in the treatment of Ménière's disease. This modality and other inner-ear medical therapy are gaining increased clinical and scientific attention. We previously described the kinetics and effects of gentamicin uptake into the inner ear after delivery of the medicine into the middle ear using a variety of different techniques and sustained-release modalities [1]. In our previous work, we reported an early peak perilymph concentration and the presence of intracellular gentamicin at the 4-hour time point. We also demonstrated the activation of inner-ear damage pathways at this early time point. In this report, we examine the kinetics of gentamicin at very early time points, 1 and 2 hours after administration. Healthy adult chinchillas underwent implantation of middle-ear sustained-release devices (one to each ear) containing gentamicin. The animals then were maintained in a neutral position and underwent perilymph gentamicin sampling at the two predetermined time points. This technique allowed us to assess accurately very early time point inner-ear gentamicin kinetics and to compare the activity. The samples then were run for concentration using mass spectrometry. The information gained from this study may increase our scientific understanding about the effects of gentamicin on the inner ear and may allow clinicians to treat patients more effectively for inner-ear disorders.
authors.affiliation: Department of Defense Spatial Orientation Center, Department of Otolaryngology, Naval Medical Center San Diego, San Diego, CA 92134-2200, USA. mehoffer@nmcsd.med.navy.mil
authors.forename: Michael E
authors.initials: ME
authors.lastname: Hoffer
authors.forename: Keith
authors.initials: K
authors.lastname: Allen
authors.forename: Kim
authors.initials: K
authors.lastname: Gottshall
authors.forename: Robert
authors.initials: R
authors.lastname: Moore
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kopke
authors.forename: Derin
authors.initials: D
authors.lastname: Wester
authors.forename: Carey
authors.initials: C
authors.lastname: Balaban
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002682:Chinchilla; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D007758:Ear, Inner / Q000187:drug effects / Q000378:metabolism*; D005839:Gentamicins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007118:Immunoassay; D013058:Mass Spectrometry / Q000379:methods; D008575:Meniere Disease / Q000188:drug therapy; D010498:Perilymph / Q000187:drug effects / Q000378:metabolism*; D010865:Pilot Projects
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D005839:Gentamicins