Fig. 1. Pharmacokinetics and pharmacodynamics of an opioid. After injection of a drug into the blood stream, it spreads across the various tissues (drug disposition). From the plasma (with concentration Cp), it crosses the blood-brain barrier to reach the effect compartment (t ½ke0= the blood effect-site equilibration half-life) with concentration Ce. At the opioid-receptor site, the drug interacts with the receptor (receptor kinetics) with a constant for receptor association (kon) and dissociation (koff), here depicted as half-lives t ½konand t ½koff. For naloxone, t ½ke0= 6.5 min and t ½koff= 0.82 min; for buprenorphine, t ½ke0= 75 min and t ½koff= 70 min; and for fentanyl, t ½ke0= 5–15 min and t ½koff< 0.1 min.