PKPD Models for Opioid Effect: which End Point Serves the Clinician Best?

Whereas the PK of a drug describes the time course of dose to concentration, the pharmacodynamics describes the concentration-to-effect relationship.
PKPD models are constructed for each drug to allow clinicians to understand and predict the clinical implication of a given dose to a desired effect. These models allow dosing regimens to be constructed based on patient characteristics such as total or lean body weight, gender, or age.
1. For most opioid effects (e.g., analgesia, sedation, and respiratory depression), the effect site is located within the central nervous system, but the effect site for constipation is the gastrointestinal tract.
2. The delay between the peak drug concentration in the plasma and the peak concentration at the effect site is described by the plasma effect-site equilibration constant k _e0 (commonly referred to as hysteresis).
The clinician should choose a PKPD model derived from a population of subjects whose characteristics are most similar to the individual they are treating (e.g., elderly patients are more sensitive to opioids, renal or liver disease may impact dosing levels).
For most opioids, the target effect when constructing PKPD models has traditionally been the slowing of the frequency components of the EEG. However, because the C ₅₀ for EEG effects occurs beyond the normal clinical dose range of opioids, more clinically useful C ₅₀ values would include those for the analgesic, respiratory depressive, and sedative effect of opioids.