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Ventilatory Response to Single, High Dose Estazolam in Healthy Humans
Author(s) -
Skatrud James B.,
Badr Safwan,
Begle Robert L.,
Juan David
Publication year - 1990
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1990.tb03618.x
Subject(s) - anesthesia , ventilation (architecture) , placebo , sedation , respiration , respiratory center , medicine , control of respiration , respiratory system , mechanical engineering , alternative medicine , pathology , engineering , anatomy
The purpose of this study was to determine the effect of oral estazolam at two and three times the usually recommended dosage (2 mg) on ventilation and respiratory drive during wakefulness. Sixty healthy subjects were randomized to receive a single oral dose of either: 1) estazolam 4 mg; 2) estazolam 6 mg; 3) placebo; or 4) morphine 0.15 mg/kg. Predrug and postdrug measurements were obtained for ventilation, respiratory cycle timing, metabolic rate, temperature, and ventilatory and mouth occlusion pressure (P0.1) responses to exogenous CO 2 . No difference between placebo and the study drugs was noted during eupneic breathing. During administration of exogenous CO 2 , morphine caused a decrease in the slope of the ventilatory (–0.4 ± 0.1 L/min/mm Hg, P = .008) and P0.1 (–0.22 ± 0.06 cm H 2 O/mm Hg, P = .015) responses. Estazolam (4 and 6 mg) had no effect on the ventilatory response to exogenous CO 2 . However, estazolam (6 mg) caused the P0.1 at a PCO 2 of 57 mm Hg to decrease (–0.67 ± 0.30 cm H 2 O, P = .005). The preservation of ventilation with the highest dose of estazolam, despite the decrease in P0.1, indicates that a compensatory strategy independent of respiratory center drive may have been activated. Sedation was a common side effect of estazolam reported in 13% and 53% of subjects at the 4 mg and 6 mg doses, respectively. We conclude that a single, high dose of estazolam does not cause ventilatory depression during wakefulness in healthy subjects.