The primary objective of the proposed work is development of a high resolution
pharmacokinetic-pharmacodynamic (PK-PD) model of hydromorphone for experimental pain stimuli,
ventilatory depression, and surrogate biomarkers of opioid effect that will allow the
fingerprinting of hydromorphone. This fingerprint will serve as the basis for the development
of dosing strategies that efficiently maximize analgesia while minimizing ventilatory
depression and sedation. For example, this high-resolution fingerprint will allow precise
estimation of an initial hydromorphone target effect site concentration (Ce) from those of
effectively administered synthetic opioids with previously determined high-resolution
fingerprints (i.e., remifentanil or fentanyl), thereby minimizing underdosing of
hydromorphone for analgesia and minimizing side effects.