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Pharmacodynamic effects of opiate receptor antagonism: An agonist challenge study
Author(s) -
Chalon S.,
Suico J. G.,
Renard D.,
Carter M. K.,
Diringer K.,
Chavers J.,
Cantrell A. S.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.11.110
Subject(s) - medicine , pharmacodynamics , blockade , crossover study , endocrinology , placebo , agonist , naltrexone , opiate , hydrocortisone , antagonist , receptor , pharmacokinetics , alternative medicine , pathology
Background Pharmacodynamic effects of opiate antagonists and agonists such as naltrexone (NTX) and fentanyl (FE) have been documented in separate studies and various populations. However, no data are available for a direct comparison in the same group of subjects. Methods NTX 50mg QD and a matched placebo were compared in a randomized double‐blind crossover study conducted in a research hospital setting. NTX was administered for 3 days to 16 healthy males. ACTH, cortisol, FSH, LH, PRL and pupillary diameter (PD) were measured on Day 1. On Day 3, blockade of agonist‐induced effects was tested by use of an IV bolus of FE. Results On Day 1, NTX induced an increase in LH, ACTH and cortisol (p<0.01 each; 90%CI ratio[1.29–1.91],[1.42–2.40],[1.26–2.06]). No effect was observed on FSH, PRL and PD. On Day 3, NTX was associated with a blockade of the following FE effects: increase in ACTH (p<0.0001,[0.15–0.59]), cortisol (p=0.01,[0.38–0.81]) and PRL (p<0.0001,[0.12–0.22]) and reduction in PD (p<0.0001,[2.47–3.32]). NTX did not influence pain perception during the cold pressor test performed after FE. Conclusion Blockade of FE‐induced changes in PRL and PD were the most significant treatment effects observed. In contrast to FE‐induced decreases in ACTH/cortisol reported in stressed or surgical patients, an increase was observed in healthy volunteers. This effect was blocked by NTX. Clinical Pharmacology & Therapeutics (2005) 77 , P28–P28; doi: 10.1016/j.clpt.2004.11.110