Pharmacokinetics and pharmacodynamics of morphinomimetics in the central nervous system

The penetration of opioids into interstitial space of the brain is related to their physicochemical properties. All opioids are weak bases with different lipid solubilities; the octanol-water partition coefficient varies from 1.4 to 1700 for morphine and sufentanil, respectively. Lipid solubility is an essential factor for diffusion capacity across the capillary walls but the rate at which drug enters the brain by simple passive diffusion is more related to the diffusible fraction (unbound, unionized) for fentanyl and its derivatives. The relative potency of the analgesic effect is related to the characteristics of the opiate receptor interaction (KD, Ki). Sufentanil is the most potent of the opioids currently available for use in man, it has a very high binding affinity for the mu-opioid receptor. The duration of the pharmacological effect is determined by the time of dissociation of stereospecific drug-receptor binding and also by pharmacokinetic half-life; the recovery would be expected in consideration of the different terminal half-times.