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Updated: Apr 7, 2026

Modeling and Simulations of Olfactory Drug Delivery with Passive and Active Controls of Nasally Inhaled Pharmaceutical Aerosols
Published on: May 20, 2016
Oral pseudoephedrine decreases the rate of transmucosal nitrous oxide exchange for the middle ear
Miriam S Teixeira1,2, Cuneyt M Alper1,2, Brian S Martin3,4
1Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Objectives/Hypothesis:
Determine if oral treatment with a vasoconstrictor decreases the blood to middle ear exchange rate of the perfusion-limited gas, nitrous oxide (N2O).
Study Design:
Randomized, double-blind, crossover study.
Methods:
Ten adult subjects with and 10 without past middle ear disease completed paired experimental sessions, identical except for oral treatment with either pseudoephedrine hydrochloride or lactose placebo. At each session, subjects were fitted with a nonrebreathing mask and breathed room air for 20 minutes (acclimation period), 50% N2O:50% O2 for 20 minutes (experimental period), and 100% O2 for 10 minutes (recovery period). Throughout, heart rate, blood pressure, and O2 saturation were monitored, and bilateral middle ear pressures were recorded by tympanometry every minute. The primary outcome was the slope of the middle ear pressure-time function for the experimental period, which estimates the volume N2O exchange rate. Using repeated measures analysis of variance, the effects of group (disease history), treatment (active vs. placebo), and period (1 vs. 2) on the recorded vital signs, and of group, treatment, and ear (left/right) on the middle ear pressure-time slope were evaluated for statistical significance.
Results:
Statistically significant effects of period on O2 saturation (period 2 > period 1) and of treatment on heart rate (active > placebo) were documented. Only treatment was statistically significant for the middle ear pressure-time slope, with a shallower slope characterizing the active treatment session.
Conclusions:
The volume exchange rate across the middle ear mucosa of perfusion-limited gases can be modulated pharmacologically. Theoretically, similar drugs can be used to reduce the requisite eustachian tube opening efficiency for adequate middle ear pressure regulation.
Level Of Evidence:
1b.
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