Effects of Morphine after Inhalation and Intravenous Administration Compared. Dershwitz et al.(page 619)

Dershwitz et al.  enrolled 15 healthy volunteers in their study to compare the pharmacokinetics and pharmacodynamics of morphine delivered via  different routes: intravenously or an aerosol delivery system. As per original protocol design, the first two volunteers were administered the lower dose of morphine: four inhalations of 2.2 mg morphine each at 1-min intervals or 4.4 mg intravenously. However, after administration of the lower dose, it became clear that the magnitude of ventilatory depressant effect was small. The remaining 13 subjects, then, were administered the higher dose of morphine: eight inhalations of 2.2 mg (17.6 mg total) or 8.8 mg intravenously over 7 min.

The study was designed to primarily measure drug onset, so researchers sampled subjects’ arterial blood during morphine administration and at regular intervals until 4 h postadministration. The effects of morphine were assessed by measuring pupil diameter and ventilatory response to a hypercapnic challenge. Pharmacokinetic and pharmacodynamic analyses were performed simultaneously using mixed-effect models. When administered via  inhalation, the total bioavailability of the morphine was 59%, 43% of which was absorbed immediately. The median times to half-maximal miotic effects of morphine were 10 min after inhalation and 5.5 min after intravenous administration. Duration of effects of morphine delivered were similar for both administration routes.