T-23: New Methodology to Evaluate a Drugs Effect on Respiratory Depression

Poster Presenter

Erik Hansen

Clinical Manager
Kalvista Pharmaceuticals
United States

Objectives

Understand how to assess a new drug in development effects on potential of causing respiratory depression and in combination with other drugs.

Method

Following IRB approval we conducted a study to validate the method of assessing respiratory depression in subjects exposed to 7% carbon dioxide, 21% oxygen and 82% nitrogen. The study was a double blind randomized 2-period crossover study in 12 healthy male volunteers.

Results

All twelve subjects completed the study. Subjects receiving oxycodone showed a mean decrease of respiratory drive after 5 minutes of breathing a hypercapnic mixture. As expected, the 12 subject average slope of the linear regression line (minute ventilation vs. end-tidal CO2) decreased by 50% under oxycodone when compared to placebo. The average minute ventilation also showed an average decrease of 27% for those receiving oxycodone. There were no significant or unexpected adverse events. Ventilatory response to hypercapnia (VRH) showed a consistent decrease in respiratory drive, as measured by the slope of the linear regression line and by minute ventilation, in subjects using oxycodone

Conclusion

Ventilatory response to hypercapnia (VRH) showed a consistent decrease in respiratory drive, as measured by the slope of the linear regression line and by minute ventilation, in subjects using oxycodone. The fixed inspiratory CO2 (FiCO2) VRH model may be an effective method to assess the potential for a drug (or a combination of drugs) to suppress respiration and contribute to overdoses.