Partial versus full agonists for opioid-mediated analgesia--focus on fentanyl and buprenorphine.
In contrast to other opioids, fentanyl and buprenorphine share a number of physicochemical properties that render both agents potentially suitable for transdermal delivery. However, there are significant differences between them in terms of their pharmacological profiles, as fentanyl is a full mu opioid receptor agonist capable of exerting a maximal response in certain tissues, while buprenorphine is a partial agonist unable to exert this maximum effect even at high doses. This review examines the hypothesis that partial opioid agonists would confer a number of benefits over full agonists, namely effective analgesia with a better tolerability and a lower propensity for addiction, with respect to fentanyl and buprenorphine. An attempt is also made to correlate clinical differences between these drugs with their respective agonist profiles and other differential pharmacokinetic/pharmacodynamic properties. Despite a dearth of directly comparative trials, the pharmacology of fentanyl and buprenorphine is well documented. Considerable data concerning buprenorphine suggest that the advantages initially espoused for partial opioid agonists are not borne out in clinical practice. Indeed, it may be postulated that full mu opioid agonists, particularly those with high selectivity and potency such as fentanyl, have a superior clinical profile and fulfill the above criteria more closely. Relative receptor binding, selectivity, potency and intrinsic efficacy of the opioids appear to be key determinants of their individual pharmacological profiles, contributing significantly to the heterogeneity of this class of analgesics.
Zuurmond
W W
WW
Department of Anaesthesiology, Academic Hospital Vrije Universiteit, Postbus 7047, 1007 MB Amsterdam, The Netherlands. wwa.zuurmond@azvu.nl
Meert
T F
TF
Noorduin
H
H
D000701:Analgesics, Opioid / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002047:Buprenorphine / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D004361:Drug Tolerance; D005283:Fentanyl / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D010146:Pain / Q000188:drug therapy; D017450:Receptors, Opioid, mu / Q000819:agonists*; D019966:Substance-Related Disorders
D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D002047:Buprenorphine; D005283:Fentanyl