118 Cardiovascular Effects and Pharmacokinetics of Intranasal Tetracaine plus Oxymetazoline

Thursday, March 22, 2012: 8 a.m. - 9:30 a.m.
Presentation Type: Oral Session
E. HERSH1, L. LEVIN1, J. CHOU1, S. SECRETO1, T. CACEK2, M. HUTCHESON3, P. MOORE4, and H. GIANNAKOPOULOS1, 1School of Dental Medicine - Oral Surgery/Pharmacology, University of Pennsylvania, Philadelphia, PA, 2Pharmacokinetics, ContractKinetica, Columbia, MO, 3Biostatistics, Tegra Analytics LLC, Doylestown, PA, 4School of Dentistry, University of Pittsburgh, Pittsburgh, PA
Objectives: This study evaluated the cardiovascular effects and pharmacokinetics of intranasal 3% tetracaine/0.05 % oxymetazoline, being developed to provide needle-free anesthesia of maxillary teeth.  

Methods: The investigators administered a proposed maximum recommended dose (18 mg tetracaine/0.3 mg oxymetazoline) as three bilateral pairs of 0.1 ml nasal sprays.  Double this dose as six bilateral sprays was administered 1-3 weeks later.  Heart rate, blood pressure and oxygen saturation were recorded.  Blood samples were drawn at baseline and for two hours following drug administration.

Results: Physiologic measures remained fairly stable throughout the two-hour period, with small but significant decreases (p < 0.05) in HR at 40 and 50 min for the 2X MRD (6.1 beats/min) and MRD (7.5  beats/min) regimens respectively, and a significant increase in DBP for the 2X MRD at 90 minutes (5.9 mm Hg). Mean SpO2 remained above 99%. Tetracaine plasma levels were undetectable in most subjects, whereas concentrations of its major metabolite PBBA from the 36 /0.6 mg dose, were approximately double that of the 18/0.3 mg dose. Oxymetazoline concentrations from the 36/0.6 mg dose were approximately 50% greater than that from the 18/0.3 mg dose with a half life of 1.72 - 2.32 hours.           

Conclusions: Intranasal tetracaine/oxymetazoline mist was generally well tolerated. Additional safety and efficacy data is required, particularly in patients with cardiovascular disease and other co-morbidities.

This study was supported by a grant from St Renatus LLC.

This abstract is based on research that was funded entirely or partially by an outside source: St Renatus LLC

Keywords: Anesthetics, Clinical trials, Delivery systems, Pain and Pharmacology