Patient-Controlled Analgesia: The Importance of Effector Site Pharmacokinetics
Opioid transit across the blood-brain barrier (BBB) and into the central nervous system (CNS) is complex and is dependent on a drug’s specific physiochemical properties, such as lipophilicity, molecular size, degree of protein binding and ionization, as well as physiological factors, such as metabolism and drug clearance. More recently, drug equilibration from the systemic circulation to the CNS has been determined to be significantly governed by a dynamic interplay between influx and efflux membrane transporter pumps and synergy between transporters and metabolizing enzymes. In combination with physicochemical and physiological factors, these transporter systems regulate CNS opioid receptor exposure and effectively determine analgesic onset, as well as the magnitude and duration of pharmacodynamic (PD) effects, including side effects. The infamous and colorful bank robber “Slick Willie” Sutton suggested that the reason he robbed banks was “because that’s where they keep the money”. Following Sutton’s lead, we should look to the CNS, not traditional venous pharmacokinetic (PK) parameters, to better understand and more appropriately select opioids and routes of administration for various clinical use scenarios.
KeywordsEfflux Transporter Effector Site Pain Relief Score Sublingual Route Rapid Distribution Phase
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