Hydrocodone is currently used in the pain management, but risks related to its abuse and misuse raise an increasing problem for health ( Kenan et al., 2012 Smith et al., 2013). The largest part of prescriptions regarding pain relievers opioid drugs are oxycodone, hydrocodone, morphine, codeine, methadone and transdermal morphine and fentanyl ( Graziani and Nisticò, 2016). Opioids are the most potent drugs producing analgesia and their use is fundamental for the clinical pain management ( Mercadante et al., 2014). In these conditions, hydrocodone showed to have positive effects in non-controlled open studies and needs to be further studied to assess the real strength of results. Weaker is the evidence of the analgesic effectiveness of ER hydrocodone on other chronic pain syndromes and non-cancer non-neuropathic chronic pain. Analysis of results of clinical studies suggests that abuse-deterrent extended-release (ER) hydrocodone formulations can be effective and they are well tolerated in the treatment of chronic low back pain. A bibliographic research was carried out (from Februto August 28, 2018) independently by two researchers (blinded to the authors and initially on results) in the major scientific databases and research engines of peer-reviewed literature on life sciences and biomedical topics, starting from January 1990 to August 2018. Moreover, the authors discuss and comment on the updated data regarding safety profile and effectiveness of hydrocodone in the treatment of chronic pain. Literature on experimental preclinical pharmacology investigating analgesic activity in laboratory animals is furtherly discussed. Pharmacokinetic aspect (terminal half-life, maximum serum concentration, and time to maximum serum concentration) of hydrocodone and the influence of metabolic genetic polymorphism in analgesic response to hydrocodone are also illustrated and commented. The purpose of the study is to summarize the preclinical and clinical characteristics of hydrocodone. It is a mu-opioid agonist predominantly metabolized to the O-demethylated product hydromorphone and to the N-demethylated product norhydrocodone. Hydrocodone is one of the most prescribed oral analgesic drugs and it is one of the most abused drugs in general population. 5Pharma.Ca Research Facility (Centro Studi Pharma.Ca), Messina, Italy.4Department of Clinical and Experimental Medicine, Azienda Ospedaliera Universitaria Policlinico “G.3Pain Therapy Unit, Grande Ospedale Metropolitano Bianchi Melacrino Morelli–Reggio Calabria, Reggio Calabria, Italy.2Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Azienda Ospedaliera Universitaria Policlinico “G.1Anesthesia, Intensive Care and Pain Therapy, Azienda Ospedaliera Universitaria Policlinico “G. Luigi Cardia 1, Gioacchino Calapai 2*, Domenico Quattrone 3, Cristina Mondello 2, Vincenzo Arcoraci 4, Fabrizio Calapai 5, Carmen Mannucci 2 and Epifanio Mondello 1
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