Respiratory study determing the utility of respiratory stimulants in healty volunteerds.

A study to determine the utility of respiratory stimulants with and without opioid therapy and with hypercapnia or ambient air.

Development and validation of a clinical Proof-of-Concept study paradigm for determing the clinical utility of respiratory stimulants over the potential therapeutic dose range in the face of opioid respiratory depression and presences of hypercapnia.

Part 1:

Ventilatory assessments: Every 30 min;

Blood Sample: 28 samples for Alfentanil, 15 samples for Doxapram;

Subjects sedation scale: Every 30 min;

Heartrate, saturation and CO will be measured continously.



Part 2:

Ventilatory assessments: Every 30 min;

Blood Sample: 17 samples for Doxapram;

Subjects sedation scale: Every 30 min;

Heartrate, saturation and CO will be measured continously.

8-16 volunteers will be included in Part 1.

In part 1 they will participate during 4 study days. In 2 study days their EtCO2 will be clamped, in 2 study days there will be ambient air and pain measurements will be performed. All 4 study days they will receive Alfentanil in 2 different doses, 2 days they will receive Doxapram in 2 different doses or a placebo.

In Part 2 6-10 patients will be included depended on the results of part 1. During part 2 the patients will receive two doses of Doxapram without Alfentanil.

Furthermore we will measure cardiac output during both parts.